Brain-derived neurotrophic factor (BDNF)

Physical activity, and specifically exercise, has shown promise as an intervention for drug addiction; however, the exercise conditions that produce the most efficacious response, as well as its underlying mechanism, are unknown. In this study, we examined the dose-dependent effects of wheel running, an animal model of exercise, during abstinence on subsequent cocaine-seeking and associated changes in prefrontal cortex (PFC) brain-derived neurotrophic factor (Bdnf) exon IV expression, a marker of epigenetic regulation implicated in cocaine relapse and known to be regulated by exercise. Cocaine-seeking was assessed under a within-session extinction/cue-induced reinstatement procedure following extended access cocaine or saline self-administration (24-h/day, 4 discrete trials/h, 10 days, 1.5 mg/kg/infusion) and a 14-day abstinence period. During abstinence, rats had either locked or unlocked running wheel access for 1, 2, or 6 h/day. Bdnf exon IV expression was assessed using quantitative real-time polymerase chain reaction. Cocaine-seeking was highest under the locked wheel condition, and wheel running dose dependently attenuated this effect. Cocaine increased Bdnf exon IV expression, and wheel running dose dependently attenuated this increase, with complete blockade in rats given 6-h/day access. Notably, the efficacy of exercise was inversely associated with Bdnf exon IV expression, and both its efficacy and its effects on Bdnf exon IV expression were mimicked by treatment during abstinence with sodium butyrate, a histone deacetylase inhibitor that, like exercise, modulates gene transcription, including Bdnf exon IV expression. Taken together, these results indicate that the efficacy of exercise is dose dependent and likely mediated through epigenetic regulation of PFC Bdnf.

Parkinson's disease (PD) has a progressive course and is characterized by the degeneration of dopaminergic neurons. Although no neuroprotective treatments for PD have been found to date, the endocannabinoid system has emerged as a promising target. From a sample of 119 patients consecutively evaluated in a specialized movement disorders outpatient clinic, we selected 21 PD patients without dementia or comorbid psychiatric conditions. Participants were assigned to three groups of seven subjects each who were treated with placebo, cannabidiol (CBD) 75 mg/day or CBD 300 mg/day. One week before the trial and in the last week of treatment participants were assessed in respect to (i) motor and general symptoms score (UPDRS); (ii) well-being and quality of life (PDQ-39); and (iii) possible neuroprotective effects (BDNF and H(1)-MRS). We found no statistically significant differences in UPDRS scores, plasma BDNF levels or H(1)-MRS measures. However, the groups treated with placebo and C...

Background: Exposure to predator scent (PS) has been used as a model of stress associated with danger to life and body integrity. Under stress conditions, the brain serotoninergic (5-HT) system plays an important role. Methods: We tested the hypothesis that repeated PS exposure alters the excitability of 5-HT neurons of the dorsal raphe nucleus. To study the mechanisms involved, we approached serum and adrenal corticosterone and aldosterone concentrations, as well as brain-derived neurotrophic factor (BDNF) expression. Adult male Sprague-Dawley rats were exposed to PS for ten minutes daily for ten consecutive days. Two weeks after the last exposure, electrophysiological and biochemical assessments were performed. Results: Measurements by in vivo electrophysiology showed increased firing activity of 5-HT neurons in rats exposed to PS. Exposure to PS resulted in reduced serum corticosterone and aldosterone concentrations. Concentrations of both corticosteroids in the adrenal glands and the relative weight of the adrenals were unaffected. The gene expression of hippocampal BDNF of rats exposed to PS remained unaltered. PS exposure failed to induce changes in the gene expression of selected adrenal steroidogenic factors. Conclusion: Reduced corticosteroid concentrations in the blood appear to be the result of increased metabolism and/or tissue uptake rather than altered steroidogenesis. The decrease in circulating corticosterone in rats who experienced repeated PS may represent part of the mechanisms leading to increased excitability of 5-HT neurons. The increase in 5-HT neuronal activity might be an important compensatory mechanism designated to diminish the harmful effects of the repeated PS exposure on the brain.

Abstract-Exercise is an important facet of behavior that enhances brain health and function. Increased expression of the plasticity molecule brain-derived neurotrophic factor (BDNF) as a response to exercise may be a central factor in exercise-derived benefits to brain function. In rodents, daily wheel-running exercise increases BDNF gene and protein levels in the hippocampus. However, in humans, exercise patterns are generally less rigorous, and rarely follow a daily consistency. The benefit to the brain of intermittent exercise is unknown, and the duration that exercise benefits endure after exercise has ended is unexplored. In this study, BDNF protein expression was used as an index of the hippocampal response to exercise. Both daily exercise and alternating days of exercise increased BDNF protein, and levels progressively increased with longer running duration, even after 3 months of daily exercise. Exercise on alternating days was as effective as daily exercise, even though exe...

A b s t r a c t Brain-derived neurotrophic factor (BDNF) plays an important role in neuro-nal survival and growth, serves as a neurotransmitter modulator, and participates in neuronal plasticity, which is essential for learning and memory. It is widely expressed in the CNS, gut and other tissues. BDNF binds to its high affinity receptor TrkB (tyrosine kinase B) and activates signal transduc-tion cascades (IRS1/2, PI3K, Akt), crucial for CREB and CBP production, that encode proteins involved in β cell survival. BDNF and insulin-like growth factor-1 have similar downstream signaling mechanisms incorporating both p-CAMK and MAPK that increase the expression of pro-survival genes. Brain-derived neurotrophic factor regulates glucose and energy metabolism and prevents exhaustion of β cells. Decreased levels of BDNF are associated with neurodegenerative diseases with neuronal loss, such as Parkinson's disease, Alzheimer's disease, multiple sclerosis and Huntington's disease. Thus, BDNF may be useful in the prevention and management of several diseases including diabetes mellitus.

The effects of the adaptive immune system on the cognitive performance and abnormal behaviors seen in mental disorders such as schizophrenia have never been documented. Here, we show that mice deprived of mature T cells manifested cognitive deficits and behavioral abnormalities, which were remediable by T cell restoration. T cell-based vaccination, using glatiramer acetate (copolymer-1, a weak agonist of numerous self-reactive T cells), can overcome the behavioral and cognitive abnormalities that accompany neurotransmitter imbalance induced by (+)dizocilpine maleate (MK-801) or amphetamine. The results, by suggesting that peripheral T cell deficit can lead to cognitive and behavioral impairment, highlight the importance of properly functioning adaptive immunity in the maintenance of mental activity and in coping with conditions leading to cognitive deficits. These findings point to critical factors likely to contribute to age- and AIDS-related dementias and might herald the developm...

The brain-derived neurotrophic factor (BDNF) is a protein mainly synthetized in the neurons. Early evidence showed that BDNF participates in cognitive processes as measured at the hippocampus. This neurotrophin is as a reliable marker of brain function; moreover, recent studies have demonstrated that BDNF participates in physiological processes such as glucose homeostasis and lipid metabolism. The BDNF has been also studied using the exercise paradigm to determine its response to different exercise modalities; therefore, BDNF is considered a new member of the exercise-related molecules. The high-intensity interval training (HIIT) is an exercise protocol characterized by low work volume performed at a high intensity [i.e., ≥80% of maximal heart rate (HRmax)]. Recent evidence supports the contention that HIIT elicits higher fat oxidation in skeletal muscle than other forms of exercise. Similarly, HIIT is a good stimulus to increase maximal oxygen uptake (VO 2 max). Few studies have investigated the impact of HIIT on the BDNF response. The present work summarizes the effects of acute and long-term HIIT on BDNF.

Strong evidence indicates that regular aerobic training induces beneficial effects on cognitive functions. The present controlled fMRI study was designed to investigate the impact of a short-term intense aerobic exercise on the pattern of functional activation during the retrieval of learned pair-associates in 17 young and healthy male adults compared to 17 matched control subjects. We further aimed to relate putative changes in hippocampal activation to postulated changes in the exercised-induced brain derived neurotrophic factor (BDNF). The supervised exercise program was performed on a bicycle ergometer and lasted six weeks, with three aerobic sessions per week. We found profound improvement of physical fitness in most subjects indicated by the target parameter 'individual anaerobic threshold'. Significant improvements in the cognitive performance were detected in the exercise group, but also in the control group. We observed significant differences in the activation patt...

Neuropathic pain (NP) is a chronic pain modality that usually results of damage in the somatosensory system. NP often shows insufficient response to classic analgesics and remains a challenge to medical treatment. The Transcranial Direct Current Stimulation (tDCS) is a non-invasive technique, which induces neuroplastic changes in central nervous system of animals and humans. The brain derived neurotrophic factor plays an important role in synaptic plasticity process. Behavior changes such as decreased locomotor and exploratory activities and anxiety disorders are common comorbidities associated with NP. Evaluate the effect of tDCS treatment on locomotor and exploratory activities, and anxiety-like behavior, and peripheral and central BDNF levels in rats submitted to neuropathic pain model. Rats were randomized divided: Ss, SsS, SsT, NP, NpS, NpT. The neuropathic pain model was induced by partial sciatic nerve compression at 14days after surgery; the tDCS treatment was initiated. The...

Major depressive disorder (MDD) is a devastating neuropsychiatric disorder encompassing a wide range of cognitive and emotional dysfunctions. The prevalence of MDD is expected to continue its growth to become the second leading cause of disease burden (after HIV) by 2030. Despite an extensive research effort, the exact etiology of MDD remains elusive and the diagnostics uncertain. Moreover, a marked inter-individual variability is observed in the vulnerability to develop depression, as well as in response to antidepressant treatment, for nearly 50% of patients. Although a genetic component accounts for some cases of MDD, it is now clearly established that MDD results from strong gene and environment interactions. Such interactions could be mediated by epigenetic mechanisms, defined as chromatin and DNA modifications that alter gene expression without changing the DNA structure itself. Some epigenetic mechanisms have recently emerged as particularly relevant molecular substrates, pro...

Objective
Temperature is a critical variable in health and disease. Thermal stressors such as heat stress elicit neuroendocrine responses including activation of the HPA axis .Heat stress is a challenge for animal and human society. It has been shown that brain monoaminergic system is changed during acute and chronic heat stress condition. Commercial and domestic poultry are very susceptible animals to the heat stress. High environmental temperature led to heat stress condition and had negative effect on physiological performance. One effect of heat stress is changed molecular and cellular mechanisms. These changes in diencephalon, as an awaking center (thalamus) and autonomic mechanisms center (hypothalamus), have profound physiological performance results. However the goal of experiment was to investigate effect of heat stress on diencephalic BDNF gene expression and blood corticostrone level.


Materials and Methods
In this experiment, 20 seven-day-old male chicks divided in 1- heat stress group (10 chicks) and 2- control group (10 chicks in normal temperature condition). Heat stress induced by 39 C◦ and continued to 5 hours. Control group temperature was 30 C◦. At the end of 5 hours duration, chicks was anesthetized with Isofluran gas and killed. Blood gathered from jugular vein. Brain dissected and diencephalon was frozen in liquid nitrogen immediately. Blood corticosterone level was measured by ELIZA method, BDNF gene expression assayed by quantitative real time PCR technique with the SYBR green method.

Results
In this experiment, heat stress significantly reduced diencephalic BDNF gene expression. However, corticosterone level significantly elevated in heat stress exposed chicks. It would be able to say that there is a relation between BDNF gene expression and blood corticosterone concentration.

Conclusions
These results showed changes in BDNF gene expression during heat stress condition is associated to blood corticosterone level elevation. Taken together, the results showed that a significant relationship between Hypothalamus-Hypophysis- Adernal cortex activity during acute heat stress condition and diencephalic BDNF gene expression as a neuroprotective agent of brain.

An increase in oxidative and nitrosative stress, pro-inflammatory cytokines, depression and stress, are common in a number of medical conditions, with these factors mediating many of their effects via the induction of indoleamine 2,3-dioxygenase, leading to tryptophan catabolite production, in turn decreasing levels of serotonin availability as a precursor for the melatoninergic pathways. Here we look at the role of these biological processes and their interactions in the etiology, course and management of migraine and endometriosis. Both conditions are considerably improved by melatonin, although the role of local melatonin production in non-pineal cells in these disorders still requires clarification. In both migraine and endometriosis, increased levels of brain-derived neurotrophic factor (BDNF) may be detrimental, suggesting that the immediate precursor of melatonin, N-acetylserotonin, which is a BDNF mimic, may also have regulatory, if not negative effects in these disorders. As such, the regulation of the NAS/melatonin ratio in an array of cell types and tissues may be of some importance to the genesis, course and treatment of a number of poorly managed medical disorders, including migraine and endometriosis.

Anxiety disorders are highly prevalent and result in low quality of life and a high social and economic cost. The efficacy of cognitive-behavioural therapy (CBT) for anxiety disorders is well established, but a substantial proportion of patients do not respond to this treatment. Understanding which genetic and environmental factors are responsible for this differential response to treatment is a key step towards "personalized medicine". Based on previous research, our objective was to test whether the BDNF Val66Met polymorphism and/or childhood maltreatment are associated with response trajectories during exposure-based CBT for panic disorder (PD). We used Growth Mixture Modeling to identify latent classes of change (response trajectories) in patients with PD (N = 97) who underwent group manualized exposure-based CBT. We conducted logistic regression to investigate the effect on these trajectories of the BDNF Val66Met polymorphism and two different types of childhood maltr...

Compelling data suggest that perturbations in microbial colonization of the gut in early-life, influences neurodevelopment and adult brain function. If this is the case, then ensuring the growth of beneficial bacteria at an early age will lead to optimal brain development and maturation. We have tested whether feeding neonatal rats daily (from post-natal days 3-21) with a galacto-oligosaccharide prebiotic (Bimuno®, BGOS) or a control solution, alters the levels of hippocampal N-Methyl-D-Aspartate receptor (NMDAR) subunits (GluN1, GluN2A, GluN2B), synaptic proteins (synaptophysin, MAP2, and GAP43) and brain-derived-neurotrophic factor (BDNF), at post-natal days 22 and 56. The administration of BGOS significantly elevated GluN2A subunits, synaptophysin and BDNF in the hippocampus of 22 day old rats. The effect was also observed on day 56 (26 days after the feeding ceased). The levels of all other proteins (GluN1, GluN2B, MAP2, GAP43) remained unaltered. Increased GluN2A, synaptophysin...

The plasticity-related gene 1 (PRG1) modulates bioactive lipids at the postsynaptic density and is a novel player in neuronal plasticity and regulation of glutamatergic transmission at principal neurons. PRG1, a neuronal molecule, is highly expressed during development and regeneration processes at the postsynaptic density, modulates synaptic lysophosphatidic acid (LPA) levels and is related to epilepsy and brain injury. In the present study, we analyzed the interaction between the synaptic molecules PRG1 and LPA2R with other plasticity-related molecules the neurotrophins. The protein levels of NGF, BDNF and NT-3 were measured using ELISA in hippocampal tissue of homozygous (PRG(-/-)) and heterozygous (PRG(+/-)) PRG1 deficient mice and compared to their wild type (PRG(+/+)/WT) littermates. In the hippocampus, protein levels of NT-3 were significantly increased in PRG(-/-) mice (compared to WT-litters) while protein levels of NGF and BDNF were not affected. Since PRG1 deficiency lead...

Notwithstanding major advances in psychotherapeutics, their efficacy and specificity remain limited. The slow onset of beneficial outcomes and numerous adverse effects of widely used medications remain of chief concern, warranting in-depth studies. The majority of frontline therapies are thought to enhance the endogenous monoaminergic drive, to initiate a cascade of events leading to lasting functional and structural plasticity. The latter also involves alterations in trophic factor signalling, including brain-derived neurotrophic factor (BDNF), NGF (nerve growth factors), vascular endothelial growth factor (VEGF), fibroblast growth factor 2 (FGF2), glial cell-derived neurotrophic factor (GDNF), and others. In several major mental disorders, emerging data suggest protective and restorative effects of trophic factors in preclinical models, when applied on their own. Antidepressant outcomes of VGF and FGF2, for instance, were shown in experimental animals, while BDNF and GDNF prove useful in the treatment of addiction, schizophrenia, and autism spectrum disorders. The main challenge with the effective translation of these and other findings in the clinic is the knowledge gap in action mechanisms with potential risks, as well as the lack of effective platforms for validation under clinical settings. Herein, we review the state-of-the-art and advances in the therapeutic use of trophic factors in several major neuropsychiatric disorders.

Chronic stress is known to affect the HPA axis. The few clinical studies which have been conducted on HPA-axis function in burnout have produced inconsistent results. The etiological relationship between sBDNF and burnout has not yet been studied. The aim of the current study was to investigate the role of BDNF and HPA axis in the neurobiology of burnout. In the current study 37 clinically diagnosed burnout participants were compared with 35 healthy controls in terms of BDNF, HPA axis, burnout symptoms, depression, anxiety and psychosomatic complaints. Basal serum cortisol, sBDNF and cortisol level after 1 mg DST was sampled. We found no significant differences in terms of HPA-axis function (for basal serum cortisol, p = 0.592; for cortisol level after 1 mg DST, p = 0.921), but we did find lowered sBDNF levels in burnout group (88.66 ± 18.15 pg/ml) as compared to healthy controls (102.18 ± 20.92 pg/ml) and the difference was statistically significant (p = 0.005). Logistic Regression Analysis revealed that emotional exhaustion (p = 0.05), depersonalization (p = 0.005) and depression (p = 0.025) were significantly associated with burnout. sBDNF levels correlated negatively with emotional exhaustion (r = −,268, p = 0.026), depersonalization (r = −,333, p = 0.005) and correlated positively with competence (r = 0.293, p = 0.015) sub-scales of burnout inventory. However, there were no significant relationships between cortisol levels and sBDNF levels (r = 0.80, p = 0.51), depression, anxiety, psychosomatic complaints and burnout inventory. Our results suggest that low BDNF might contribute to the neurobiology of burnout syndrome and it seems to be associated with burnout symptoms including altered mood and cognitive functions.

Strong evidence indicates that regular aerobic training induces beneficial effects on cognitive functions. The present controlled fMRI study was designed to investigate the impact of a short-term intense aerobic exercise on the pattern of functional activation during the retrieval of learned pair-associates in 17 young and healthy male adults compared to 17 matched control subjects. We further aimed to relate putative changes in hippocampal activation to postulated changes in the exercised-induced brain derived neurotrophic factor (BDNF). The supervised exercise program was performed on a bicycle ergometer and lasted six weeks, with three aerobic sessions per week. We found profound improvement of physical fitness in most subjects indicated by the target parameter 'individual anaerobic threshold'. Significant improvements in the cognitive performance were detected in the exercise group, but also in the control group. We observed significant differences in the activation patt...

The molecular basis of vulnerability to stress during the adolescent period is largely unknown. To identify potential molecular mediators that may play a role in stress-induced behavioral deficits, we imposed social isolation on a genetically vulnerable mouse model. We report that 3-week (5-8 weeks of age) adolescent stress in combination with disrupted-in-schizophrenia 1 (Disc1) genetic risk elicits alterations in DNA methylation of a specific set of genes, tyrosine hydroxylase, brain-derived neurotrophic factor and FK506 binding protein 5. The epigenetic changes in the mesocortical dopaminergic neurons were prevented when animals were treated with a glucocorticoid receptor (GR) antagonist RU486 during social isolation, which implicates the role for glucocorticoid signaling in this pathological event. We define the critical period of GR intervention as the first 1-week period during the stress regimen, suggesting that this particular week in adolescence may be a specific period of ...

Memantine (MN), a NMDA blocker is well known for its protective effect against various neurodegenerative diseases. However, its role in improving motor function and regulation of neurotrophic factors in Huntington's disease (HD) has not been studied yet. In the present study, we have investigated the effect of MN against 3-nitropropionic acid (3NP), induced motor impairment, and alterations in the expression of brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF) in mice brain. Further, its role in mitochondrial function was assessed by measuring succinate dehydrogenase (SDH) activity. Glial fibrillary acidic protein (GFAP) and neuronal nuclei (NeuN) immunoreactivity were studied to evaluate the role of MN on glial and neuronal function. Its effect on apoptosis was adjudged by studying the expression of apoptotic markers. MN restored motor functions with an associated up-regulation in neurotrophin expression. MN also enhanced brain SDH activity and decreased glutamate content. MN ameliorated striatal neuronal loss, reduced GFAP immunoreactivity, and exhibited protective effect against neuronal apoptosis. Data from the current study demonstrated that MN exerted neuroprotective effect against 3NP induced neuropathology. Restoration of motor function by MN might be through regulation of neurotrophin expression. MN can therefore be a useful therapeutic choice in the symptomatic management of HD.

Acute bouts of intense exercise increase lactate concentration, which in turn stimulates brain-derived neurotrophic factor (BDNF) production. Cortisol released during intense exercise might inhibit BDNF synthesis. This study examined the acute effects of 2 protocols of strenuous exercise on serum BDNF. Seventeen physically-active healthy females (Age = 20.0 ± 0.9 yr., BMI = 23.0 ± 2.6 kg/m2) performed a strenuous cycle-ergometer graded exercise test (GXT) and a high-intensity interval training session (HIIT). Serum BDNF, serum cortisol, cortisol: BDNF ratio and blood lactate (BLa) were recorded at baseline and immediately following exercise. Although non-statistically significant, the HIIT session elicited a higher magnitude of change from baseline for BDNF ( d = 0.17) and cortisol ( d = 1.18) than after the GXT ( d = -0.26, and d = 0.82, respectively). An interaction was found between GXT and HIIT trials and measurements on BLa levels, with higher post-exertion values after HIIT th...

Background: Recent studies in the field of Fertomaternal Medicine show that stimulation in the uterus can support brain growth and development. If in previous studies stimulation using several types of music, this study uses human voice which aims to analyze the effect of stimulation of male and female voices on differences in the expression of Brain Derived Neutrotrophic Factor (BDNF) in cerebellum of newborn Rattus norvegicus. Methods: This type of research is true experimental with post test only control group design. Rattus norvegicus was given stimulation of men voice and women voice on 6 th day until 17 th day of pregnancy. The expression of BDNF was examined using immunohistochemistry. Results: The mean ± standard deviation of the expression of BDNF in the cerebellum is 4.20 ± 1.75 (without stimulation), 6.04 ± 1.58 (male voice stimulation), and 5.60 ± 2.43 (female voice stimulation). The results of statistical tests show that there is a significant difference on BDNF expression between the control group and the group stimulated with male voice with a significance value <0.05 of 0.045 Conclusion: Giving stimulation using the male voice during pregnancy shows a significant increase in the expression of BDNF in cerebellum of newborn Rattus norvegicus.

AbstrAct Introduction Brain-derived neurotrophic factor (BDNF) plays a crucial role in neurodevelopment, synaptic plasticity and neuronal function and survival. Serum and plasma BDNF levels are moderately, but consistently, decreased in patients with schizophrenia (SCZ) compared with healthy controls. There is a lack of knowledge, however, on the temporal manifestation of this decline. Clinical, illness course and treatment factors might influence the variation of BDNF serum levels in patients with psychosis. In this context, we propose a longitudinal study of a cohort of SCZ and schizophrenic and schizoaffective disorder (SAD) Sardinian patients with the aim of disentangling the relationship between peripheral BDNF serum levels and changes of psychopathology, cognition and drug treatments. Methods and analysis Longitudinal assessment of BDNF in Sardinian psychotic patients (LABSP) is a 24-month observational prospective cohort study. Patients with SAD will be recruited at the Psychiatry

Reduction of the protein content from 25 to 8% casein in the diet of pregnant rats results in impaired neocortical long-term potentiation (LTP) of the offspring together with lower visuospatial memory performance. The present study was aimed to investigate whether this type of maternal malnutrition could result in modification of plastic capabilities of the entorhinal cortex (EC) in the adult progeny. Unlike normal eutrophic controls, 55–60-day-old prenatally malnourished rats were unable to develop LTP in the medial EC to tetanizing stimulation delivered to either the ipsilateral occipital cortex or the CA1 hippocampal region. Tetanizing stimulation of CA1 also failed to increase the concentration of brain-derived neurotrophic factor (BDNF) in the EC of malnourished rats. Impaired capacity of the EC of prenatally malnourished rats to develop LTP and to increase BDNF levels during adulthood may be an important factor contributing to deficits in learning performance having adult pren...

The effect of intracerebroventricular injection of the mitosis inhibitor colchicine on expression of mRNA for nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin 3 was studied in the rat brain with in situ hybridization. Colchicine up-regulates mRNA for NGF and BDNF in many of the neuronal systems normally expressing these factors. In addition, after colchicine treatment NGF and BDNF mRNAs were localized in several brain areas where they normally cannot be detected. Thus, NGF mRNA was present, for example, in many motor nuclei and in the basal forebrain, and BDNF mRNA was seen in many nuclei in the brain stem and in catecholamine neurons, including dopamine neurons in the substantia nigra. The latter neurons have recently been shown to be sensitive to BDNF, and the present results show that these neurons can produce this factor themselves. A decrease in mRNA for BDNF and neurotrophin 3 was seen only in the granular-cell layer of the hippocampal form...