In the present study we demonstrate that propionic acid (PA), a metabolite that accumulates in la... more In the present study we demonstrate that propionic acid (PA), a metabolite that accumulates in large amounts in propionic acidemia, is able to decrease in vitro incorporation of [32P]ATP into neurofilament subunits (NF-M and NF-L) and alpha- and beta-tubulin. Considering that the endogenous phosphorylating system associated with the cytoskeletal fraction contains cAMP-dependent protein kinase (PKA), Ca2+/calmodulin protein kinase II (CaMKII), and protein phosphatase 1 (PP1), we first assayed the effect of the acid on the kinase activities by using the specific activators cAMP and Ca2+/calmodulin or the inhibitors PKAI or KN-93 for PKA and CaMKII, respectively. Results demonstrated that the acid totally inhibited the stimulatory effect of cAMP and interfered with the inhibitory effect of PKAI. In addition, PA partially prevented the stimulatory effect of Ca2+/calmodulin and interfered with the effect of KN-93. In addition, we demonstrated that PA totally inhibited in vitro dephosphorylation of neurofilament subunits and tubulins mediated by PP1 in brain slices pretreated with the acid. Taken together, these results demonstrate that PA inhibits the in vitro activities of PKA, CaMKII, and PP1 associated with the cytoskeletal fraction of the cerebral cortex of rats. This study suggests that PA at the same concentrations found in tissues from propionic acidemic children may alter phosphorylation of cytoskeletal proteins, which may contribute to the neurological dysfunction characteristic of propionic acidemia.
Archives of Gerontology and Geriatrics, Mar 1, 2022
OBJECTIVE To systematically review the acute effects of physical exercise on memory in healthy el... more OBJECTIVE To systematically review the acute effects of physical exercise on memory in healthy elderly people. METHODS The present study consists of a systematic review based on the criteria of the Preferred Reporting Items for Systematic Reviews and Meta - Analyzes (PRISMA). Searches were carried out in the health databases: PubMed (Medline); ScienceDirect (Elsevier); SciELO, Cochrane and LILACS, including articles published until April 2021. The included studies should be randomized clinical trials in healthy elderly populations, have acute physical exercise as an intervention compared to another type of exercise or to a control session, and assess memory as an outcome. RESULTS A total of 3711 records were found in the databases. After reading titles and abstracts, 27 full texts of studies were selected. A total of 10 records met the inclusion criteria and were considered eligible for qualitative analysis. The total sample consisted of 465 healthy individuals, of both sexes, aged between 60 and 95 years. The aerobic and resistance exercises performed at low (7-11 Borg scale, 54% FCM or 40-54% 1RM) and moderate intensities (12-15 Borg scale, 50-70% FCM and 55-75% 1RM) lead to memory improvement in cognitively healthy elderly people. CONCLUSIONS The paucity of studies with this population, using higher exercise intensities, as well as a reduced variety of memory tests, were limiting factors. Maintaining a training routine is important, in order to preserve physical and mental health. More studies addressing the effects of exercise protocols in healthy individuals are warranted.
Neurofunctional deficits in mice induced by postnatal iron exposure: dose, time and MPTP interact... more Neurofunctional deficits in mice induced by postnatal iron exposure: dose, time and MPTP interactions. In: Palomo T, Beninger RJ, Archer T (eds). Neurdegerative Brain Disorders
Cns & Neurological Disorders-drug Targets, Jun 1, 2023
: It is believed that degenerative conditions that give rise to neurological diseases may share a... more : It is believed that degenerative conditions that give rise to neurological diseases may share an abnormal influx of Ca2+, mainly through glutamate receptors. Current research on the glutamatergic system indicates that the N-methyl-D-aspartate receptor (NMDAR) is not the only receptor permeable to Ca2+. Under certain conditions, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) are able to rapidly and potently mediate a neurotoxic Ca2+ influx. AMPARs are encoded by four genes designated GluR 1-4. The presence of the edited GluA2 subunit makes the heteromeric AMPAR impermeable to Ca2+ (CI-AMPAR's). On the other hand, the lack of GluA2 or disruptions in its post-translational editing result in Ca2+-permeable AMPA receptors (CP-AMPARs). In addition to triggering behavioral changes, the increase in CP-AMPARs is documented in several neurodegenerative, neuroinflammatory and neurotoxic conditions, demonstrating that AMPAR changes may play a role in the emergence and evolution of pathological conditions of the central nervous system (CNS). Seeking to better understand how CP-AMPARs influence CNS neuropathology, and how it may serve as a pharmacological target for future molecules, in this article, we summarize and discuss studies investigating changes in the composition of AMPARs and their cellular and molecular effects, to improve the understanding of the therapeutic potential of the CP-AMPAR in neurodegenerative, neurotoxic and neuroinflammatory diseases.
Clinical and preclinical evidence has indicated that estrogen depletion leads to memory impairmen... more Clinical and preclinical evidence has indicated that estrogen depletion leads to memory impairments and increases the susceptibility to neural damage. Here, we have sought to investigate the effects of Cannabidiol (CBD) a non-psychotomimetic compound from Cannabis sativa, on memory deficits induced by estrogen depletion in rats, and its underlying mechanisms. Adult rats were subjected to bilateral ovariectomy, an established estrogen depletion model in rodents, or sham surgery and allowed to recover for three weeks. After that, they received daily injections of CBD (10 mg/kg) for fourteen days. Rats were tested in the inhibitory avoidance task, a type of emotionally-motivated memory. After behavioral testing they were euthanized, and their hippocampi were isolated for analysis of components of the Akt/GSK3β survival pathway and the antiapoptotic protein Bcl2. Results revealed that ovariectomy impaired avoidance memory, and CBD was able to completely reverse estrogen depletion-induced memory impairment. Ovariectomy also reduced Akt/GSK3β pathway's activation by decreasing the phosphorylation levels of Akt and GSK3β and Bcl2 levels, which were ameliorated by CBD. The present results indicate that CBD leads to a functional recovery accompanied by the Akt/GSK3β survival pathway's activation, supporting its potential as a treatment for estrogen decline-induced deterioration of neural functioning and maintenance.
Iron overload contributes to the development of neurodegeneration and the exacerbation of normal ... more Iron overload contributes to the development of neurodegeneration and the exacerbation of normal apoptosis rates, largely due to its participation in the Fenton reaction and production of reactive oxygen species (ROS). Mitochondria constitute the major intracellular source of ROS and the main target of attack by free radicals. They are dynamic organelles that bind (fusion) and divide (fission) in response to environmental stimuli, developmental status, and energy needs of the cells. Sulforaphane (SFN) is a natural compound that displays antioxidant and anti-inflammatory activities. This study aims to investigate the effects of SFN on memory deficits and changes in markers of mitochondrial function, DNM1L and OPA1, and the synaptic marker, synaptophysin, induced by neonatal iron treatment. Male rats received vehicle or carbonyl iron (30mg/kg) from the 12th to the 14th postnatal day. In adulthood, they were treated with saline or SFN (0.5 or 5 mg/kg) for 14 days every other day. Memor...
In the present study we demonstrate that propionic acid (PA), a metabolite that accumulates in la... more In the present study we demonstrate that propionic acid (PA), a metabolite that accumulates in large amounts in propionic acidemia, is able to decrease in vitro incorporation of [32P]ATP into neurofilament subunits (NF-M and NF-L) and alpha- and beta-tubulin. Considering that the endogenous phosphorylating system associated with the cytoskeletal fraction contains cAMP-dependent protein kinase (PKA), Ca2+/calmodulin protein kinase II (CaMKII), and protein phosphatase 1 (PP1), we first assayed the effect of the acid on the kinase activities by using the specific activators cAMP and Ca2+/calmodulin or the inhibitors PKAI or KN-93 for PKA and CaMKII, respectively. Results demonstrated that the acid totally inhibited the stimulatory effect of cAMP and interfered with the inhibitory effect of PKAI. In addition, PA partially prevented the stimulatory effect of Ca2+/calmodulin and interfered with the effect of KN-93. In addition, we demonstrated that PA totally inhibited in vitro dephosphorylation of neurofilament subunits and tubulins mediated by PP1 in brain slices pretreated with the acid. Taken together, these results demonstrate that PA inhibits the in vitro activities of PKA, CaMKII, and PP1 associated with the cytoskeletal fraction of the cerebral cortex of rats. This study suggests that PA at the same concentrations found in tissues from propionic acidemic children may alter phosphorylation of cytoskeletal proteins, which may contribute to the neurological dysfunction characteristic of propionic acidemia.
Archives of Gerontology and Geriatrics, Mar 1, 2022
OBJECTIVE To systematically review the acute effects of physical exercise on memory in healthy el... more OBJECTIVE To systematically review the acute effects of physical exercise on memory in healthy elderly people. METHODS The present study consists of a systematic review based on the criteria of the Preferred Reporting Items for Systematic Reviews and Meta - Analyzes (PRISMA). Searches were carried out in the health databases: PubMed (Medline); ScienceDirect (Elsevier); SciELO, Cochrane and LILACS, including articles published until April 2021. The included studies should be randomized clinical trials in healthy elderly populations, have acute physical exercise as an intervention compared to another type of exercise or to a control session, and assess memory as an outcome. RESULTS A total of 3711 records were found in the databases. After reading titles and abstracts, 27 full texts of studies were selected. A total of 10 records met the inclusion criteria and were considered eligible for qualitative analysis. The total sample consisted of 465 healthy individuals, of both sexes, aged between 60 and 95 years. The aerobic and resistance exercises performed at low (7-11 Borg scale, 54% FCM or 40-54% 1RM) and moderate intensities (12-15 Borg scale, 50-70% FCM and 55-75% 1RM) lead to memory improvement in cognitively healthy elderly people. CONCLUSIONS The paucity of studies with this population, using higher exercise intensities, as well as a reduced variety of memory tests, were limiting factors. Maintaining a training routine is important, in order to preserve physical and mental health. More studies addressing the effects of exercise protocols in healthy individuals are warranted.
Neurofunctional deficits in mice induced by postnatal iron exposure: dose, time and MPTP interact... more Neurofunctional deficits in mice induced by postnatal iron exposure: dose, time and MPTP interactions. In: Palomo T, Beninger RJ, Archer T (eds). Neurdegerative Brain Disorders
Cns & Neurological Disorders-drug Targets, Jun 1, 2023
: It is believed that degenerative conditions that give rise to neurological diseases may share a... more : It is believed that degenerative conditions that give rise to neurological diseases may share an abnormal influx of Ca2+, mainly through glutamate receptors. Current research on the glutamatergic system indicates that the N-methyl-D-aspartate receptor (NMDAR) is not the only receptor permeable to Ca2+. Under certain conditions, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) are able to rapidly and potently mediate a neurotoxic Ca2+ influx. AMPARs are encoded by four genes designated GluR 1-4. The presence of the edited GluA2 subunit makes the heteromeric AMPAR impermeable to Ca2+ (CI-AMPAR's). On the other hand, the lack of GluA2 or disruptions in its post-translational editing result in Ca2+-permeable AMPA receptors (CP-AMPARs). In addition to triggering behavioral changes, the increase in CP-AMPARs is documented in several neurodegenerative, neuroinflammatory and neurotoxic conditions, demonstrating that AMPAR changes may play a role in the emergence and evolution of pathological conditions of the central nervous system (CNS). Seeking to better understand how CP-AMPARs influence CNS neuropathology, and how it may serve as a pharmacological target for future molecules, in this article, we summarize and discuss studies investigating changes in the composition of AMPARs and their cellular and molecular effects, to improve the understanding of the therapeutic potential of the CP-AMPAR in neurodegenerative, neurotoxic and neuroinflammatory diseases.
Clinical and preclinical evidence has indicated that estrogen depletion leads to memory impairmen... more Clinical and preclinical evidence has indicated that estrogen depletion leads to memory impairments and increases the susceptibility to neural damage. Here, we have sought to investigate the effects of Cannabidiol (CBD) a non-psychotomimetic compound from Cannabis sativa, on memory deficits induced by estrogen depletion in rats, and its underlying mechanisms. Adult rats were subjected to bilateral ovariectomy, an established estrogen depletion model in rodents, or sham surgery and allowed to recover for three weeks. After that, they received daily injections of CBD (10 mg/kg) for fourteen days. Rats were tested in the inhibitory avoidance task, a type of emotionally-motivated memory. After behavioral testing they were euthanized, and their hippocampi were isolated for analysis of components of the Akt/GSK3β survival pathway and the antiapoptotic protein Bcl2. Results revealed that ovariectomy impaired avoidance memory, and CBD was able to completely reverse estrogen depletion-induced memory impairment. Ovariectomy also reduced Akt/GSK3β pathway's activation by decreasing the phosphorylation levels of Akt and GSK3β and Bcl2 levels, which were ameliorated by CBD. The present results indicate that CBD leads to a functional recovery accompanied by the Akt/GSK3β survival pathway's activation, supporting its potential as a treatment for estrogen decline-induced deterioration of neural functioning and maintenance.
Iron overload contributes to the development of neurodegeneration and the exacerbation of normal ... more Iron overload contributes to the development of neurodegeneration and the exacerbation of normal apoptosis rates, largely due to its participation in the Fenton reaction and production of reactive oxygen species (ROS). Mitochondria constitute the major intracellular source of ROS and the main target of attack by free radicals. They are dynamic organelles that bind (fusion) and divide (fission) in response to environmental stimuli, developmental status, and energy needs of the cells. Sulforaphane (SFN) is a natural compound that displays antioxidant and anti-inflammatory activities. This study aims to investigate the effects of SFN on memory deficits and changes in markers of mitochondrial function, DNM1L and OPA1, and the synaptic marker, synaptophysin, induced by neonatal iron treatment. Male rats received vehicle or carbonyl iron (30mg/kg) from the 12th to the 14th postnatal day. In adulthood, they were treated with saline or SFN (0.5 or 5 mg/kg) for 14 days every other day. Memor...
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Papers by Nadja Schroder