Cumulative exposure to multiple early life stressors are expected to affect behavioral developmen... more Cumulative exposure to multiple early life stressors are expected to affect behavioral development causing increased susceptibility towards neuropsychiatric disorders. The present study was designed to mimic such conditions in rat model to study behavioral impairments during adolescence and adulthood. Female Wistar rats (n=32; 140-150 gm) were switched to low protein (LP; 8% protein) or Control (20% protein) diet, 15 days prior to conception and then diet regime was maintained throughout the experimental period. Pups born to Control and LP dams were intraperitoneally injected with deltamethrin (DLT-pyrethroid insecticide; 0.7mg/kg body weight; PND 1 to 7) or lipopolysaccharide (LPS-bacterial endotoxin; 0.3mg/kg body weight; PND 3 and 5) or DLT+LPS, on designated days forming 8 experimental groups (Control, LP, Control+LPS, LP+LPS, Control+DLT, LP+DLT, Control+DLT+LPS and LP+DLT+LPS). Neurobehavioral assessments were performed in F1 rats (1, 3, 6 months) by Open field, Elevated plus maze, Light and Dark box, and Rotarod tests. LP rats were found to be more susceptible to either singular or cumulative exposure as compared to their age matched control counterparts, showing significantly severe behavioural abnormalities, as hyperactivity, attention deficits, impulsiveness and low anxiety, the hallmark symptoms of neuropsychiatric disorders like schizophrenia and ADHD, suggesting thereby that early life multi-hit exposure may predispose individuals to developmental disorders.
Cumulative exposure to multiple early life stressors is expected to affect behavioral development... more Cumulative exposure to multiple early life stressors is expected to affect behavioral development, causing increased susceptibility to neuropsychiatric disorders. The present study was designed to mimic such conditions in a rat model to study behavioral impairments during adolescence and adulthood. Female Wistar rats (n = 32; 140–150 gm) were switched to a low protein (LP; 8% protein) or control (20% protein) diet 15 days prior to conception, and then the diet regime was maintained throughout the experimental period. Pups born to control and LP dams were intraperitoneally injected with deltamethrin (DLT—pyrethroid insecticide; 0.7 mg/kg body weight; PND 1 to 7), lipopolysaccharide (LPS—bacterial endotoxin; 0.3 mg/kg body weight; PND 3 and 5), or DLT+LPS, on designated days forming eight experimental groups (Control, LP, Control+LPS, LP+LPS, Control+DLT, LP+DLT, Control+DLT+LPS and LP+DLT+LPS). Neurobehavioral assessments were performed in F1 rats (1, 3, 6 months) by open field, elev...
739-748Spirulina platensis treatment (400 mg kg-1 for 25 days) effectively suppressed peripheral ... more 739-748Spirulina platensis treatment (400 mg kg-1 for 25 days) effectively suppressed peripheral sensitization via modulation of glial activation and improved motor coordination and restoration of functional motor activity in collagen-induced arthritic rats. Spirulina treatment also resulted in an appreciable reduction of the NF200 accumulation in the spinal cord neurons of arthritic rats. This is indicative of neuroprotective action of S. platensis against glutamate excitotoxicity-induced central sensitization produced by the peripheral joint inflammation in the collagen-induced arthritis. The results suggest that effects of S. platensis may be due to its counter regulation of spinal glial activation and could be a potential strategy for the treatment of arthritis
ABSTRACT Background / Purpose: Early life infection is known to activate immune responses in the ... more ABSTRACT Background / Purpose: Early life infection is known to activate immune responses in the brain that may result in the development of various psychiatric and neurodegenerative disorders in later life. We aim to investigate the molecular underpinnings of early life infection on synaptic plasticity and neurotransmitter receptor sensitivity. Main conclusion: Overexpression of NARP, Homer1a and Egr1 have implications in impairment in maintenance of LTP, poor spatial working memory and imbalance of protein degradation and synthesis, respectively.Decreased (p less than 0.05) sensitivity of striatal DA-D2R are underlying factors for developing addiction-promoting behaviours.
Protein malnourishment and immune stress are potent perinatal stressors, encountered by children ... more Protein malnourishment and immune stress are potent perinatal stressors, encountered by children born under poor socioeconomic condition. Thus, it is necessary to investigate how such stressors synergistically contribute towards developing neurological disorders in affected individuals. Pups from Wistar females, maintained on normal (high protein:HP:20%) and low protein (LP:8%) diets were used. Single and combined exposures of Poly I:C (viral mimetic:5mg/kg body wt.) and LPS (bacterial endotoxin:0.3 mg/kg body wt.) were injected to both HP and LP pups at postnatal day (PND) 3 and 9 respectively, creating 8 groups: HP (control), HP+Poly I:C, HP+LPS, HP+Poly I:C+LPS, LP, LP+Poly I:C, LP+LPS, LP+Poly I:C+LPS (multi-hit). The effects of stressors on hippocampal cytoarchitecture and behavioral abilities were studied at PND 180. LP animals were found vulnerable to immune stressors then HP animals and symptoms like neuronal damage, spine loss, downregulation of Egr 1 and Arc proteins, glio...
doi: 10.3389/fncel.2014.00355 Experimentally induced diabetes causes glial activation, glutamate ... more doi: 10.3389/fncel.2014.00355 Experimentally induced diabetes causes glial activation, glutamate toxicity and cellular damage leading to changes in motor function
A study was undertaken on the age-associated histochemical changes in the ventricular myocardium ... more A study was undertaken on the age-associated histochemical changes in the ventricular myocardium and the influence of meclophenoxate hydrochloride (MPH) on the age pigment lipofuscin. Sixty Wistar albino rats in three age-groups (3, 15 and 30 months old) were treated with meclophenoxate hydrochloride (100 mg/kg body wt/day, ip) for a period of 2-8 wk. Five animals each from the three age-groups served as controls. Various histochemical and micromorphometric studies were carried out on the myocardial tissue. A linear increase in the myocardial volume occupied by the pigment was observed with advancing age. As a result of meclophenoxate treatment, a gradual decrease in the myocardial volume occupied by the pigment was noted. After 4-6 wk treatment, the pigment bodies were found lodged into the capillary endothelium and the lumen, facilitating the removal of the pigment via blood stream. Histochemical and micromorphometric analyses of ventricular myocardium of albino rats have shown th...
Impairments in oligodendrocyte development and resultant myelination deficits appear as a common ... more Impairments in oligodendrocyte development and resultant myelination deficits appear as a common denominator to all neurological diseases. An optimal in utero environment is obligatory for normal fetal brain development and later life brain functioning. Late embryonic and early postnatal brains from F1 rat born to protein malnourished mothers were studied through a combination of immunocytochemical and quantitative PCR assay for analyzing the relative expression of platelet-derived growth factor receptor-α (PDGFRα), myelin-associated glycoprotein (MAG), proteolipid protein (PLP), and myelin oligodendrocyte glycoprotein (MOG) to determine oligodendrocyte genesis, differentiation, maturation, and myelination. Myelin integrity and corpus callosum caliber was assessed by Luxol fast blue (LFB) staining, whereas grip strength test and open field activity monitoring for behavioral evaluation in F1 rats. We demonstrate that intra-generational protein deprivation results in drastically low PDGFRα+ oligodendrocyte precursor (OPC) population and significantly reduced expression of myelin protein genes resulting in poor pre-myelinating and mature myelinating oligodendrocyte number, hypo-myelination, and misaligned myelinated fibers. LFB staining and MOG immunolabeling precisely revealed long-term changes in corpus callosum (CC) caliber and demyelination lesions in LP brain supporting the behavioral and cognitive changes at early adolescence and adulthood following maternal protein malnutrition (PMN). Thus, intra-generational PMN negatively affects the oligodendrocyte development and maturation resulting in myelination impairments and associated with behavioral deficits typically mimicking clinical hallmarks of neuropsychiatric disorders. Our results further strengthen and augment the hypothesis “Impaired gliogenesis is a big hit for neuropsychiatric phenotype.”
Cumulative exposure to multiple early life stressors are expected to affect behavioral developmen... more Cumulative exposure to multiple early life stressors are expected to affect behavioral development causing increased susceptibility towards neuropsychiatric disorders. The present study was designed to mimic such conditions in rat model to study behavioral impairments during adolescence and adulthood. Female Wistar rats (n=32; 140-150 gm) were switched to low protein (LP; 8% protein) or Control (20% protein) diet, 15 days prior to conception and then diet regime was maintained throughout the experimental period. Pups born to Control and LP dams were intraperitoneally injected with deltamethrin (DLT-pyrethroid insecticide; 0.7mg/kg body weight; PND 1 to 7) or lipopolysaccharide (LPS-bacterial endotoxin; 0.3mg/kg body weight; PND 3 and 5) or DLT+LPS, on designated days forming 8 experimental groups (Control, LP, Control+LPS, LP+LPS, Control+DLT, LP+DLT, Control+DLT+LPS and LP+DLT+LPS). Neurobehavioral assessments were performed in F1 rats (1, 3, 6 months) by Open field, Elevated plus maze, Light and Dark box, and Rotarod tests. LP rats were found to be more susceptible to either singular or cumulative exposure as compared to their age matched control counterparts, showing significantly severe behavioural abnormalities, as hyperactivity, attention deficits, impulsiveness and low anxiety, the hallmark symptoms of neuropsychiatric disorders like schizophrenia and ADHD, suggesting thereby that early life multi-hit exposure may predispose individuals to developmental disorders.
Cumulative exposure to multiple early life stressors is expected to affect behavioral development... more Cumulative exposure to multiple early life stressors is expected to affect behavioral development, causing increased susceptibility to neuropsychiatric disorders. The present study was designed to mimic such conditions in a rat model to study behavioral impairments during adolescence and adulthood. Female Wistar rats (n = 32; 140–150 gm) were switched to a low protein (LP; 8% protein) or control (20% protein) diet 15 days prior to conception, and then the diet regime was maintained throughout the experimental period. Pups born to control and LP dams were intraperitoneally injected with deltamethrin (DLT—pyrethroid insecticide; 0.7 mg/kg body weight; PND 1 to 7), lipopolysaccharide (LPS—bacterial endotoxin; 0.3 mg/kg body weight; PND 3 and 5), or DLT+LPS, on designated days forming eight experimental groups (Control, LP, Control+LPS, LP+LPS, Control+DLT, LP+DLT, Control+DLT+LPS and LP+DLT+LPS). Neurobehavioral assessments were performed in F1 rats (1, 3, 6 months) by open field, elev...
739-748Spirulina platensis treatment (400 mg kg-1 for 25 days) effectively suppressed peripheral ... more 739-748Spirulina platensis treatment (400 mg kg-1 for 25 days) effectively suppressed peripheral sensitization via modulation of glial activation and improved motor coordination and restoration of functional motor activity in collagen-induced arthritic rats. Spirulina treatment also resulted in an appreciable reduction of the NF200 accumulation in the spinal cord neurons of arthritic rats. This is indicative of neuroprotective action of S. platensis against glutamate excitotoxicity-induced central sensitization produced by the peripheral joint inflammation in the collagen-induced arthritis. The results suggest that effects of S. platensis may be due to its counter regulation of spinal glial activation and could be a potential strategy for the treatment of arthritis
ABSTRACT Background / Purpose: Early life infection is known to activate immune responses in the ... more ABSTRACT Background / Purpose: Early life infection is known to activate immune responses in the brain that may result in the development of various psychiatric and neurodegenerative disorders in later life. We aim to investigate the molecular underpinnings of early life infection on synaptic plasticity and neurotransmitter receptor sensitivity. Main conclusion: Overexpression of NARP, Homer1a and Egr1 have implications in impairment in maintenance of LTP, poor spatial working memory and imbalance of protein degradation and synthesis, respectively.Decreased (p less than 0.05) sensitivity of striatal DA-D2R are underlying factors for developing addiction-promoting behaviours.
Protein malnourishment and immune stress are potent perinatal stressors, encountered by children ... more Protein malnourishment and immune stress are potent perinatal stressors, encountered by children born under poor socioeconomic condition. Thus, it is necessary to investigate how such stressors synergistically contribute towards developing neurological disorders in affected individuals. Pups from Wistar females, maintained on normal (high protein:HP:20%) and low protein (LP:8%) diets were used. Single and combined exposures of Poly I:C (viral mimetic:5mg/kg body wt.) and LPS (bacterial endotoxin:0.3 mg/kg body wt.) were injected to both HP and LP pups at postnatal day (PND) 3 and 9 respectively, creating 8 groups: HP (control), HP+Poly I:C, HP+LPS, HP+Poly I:C+LPS, LP, LP+Poly I:C, LP+LPS, LP+Poly I:C+LPS (multi-hit). The effects of stressors on hippocampal cytoarchitecture and behavioral abilities were studied at PND 180. LP animals were found vulnerable to immune stressors then HP animals and symptoms like neuronal damage, spine loss, downregulation of Egr 1 and Arc proteins, glio...
doi: 10.3389/fncel.2014.00355 Experimentally induced diabetes causes glial activation, glutamate ... more doi: 10.3389/fncel.2014.00355 Experimentally induced diabetes causes glial activation, glutamate toxicity and cellular damage leading to changes in motor function
A study was undertaken on the age-associated histochemical changes in the ventricular myocardium ... more A study was undertaken on the age-associated histochemical changes in the ventricular myocardium and the influence of meclophenoxate hydrochloride (MPH) on the age pigment lipofuscin. Sixty Wistar albino rats in three age-groups (3, 15 and 30 months old) were treated with meclophenoxate hydrochloride (100 mg/kg body wt/day, ip) for a period of 2-8 wk. Five animals each from the three age-groups served as controls. Various histochemical and micromorphometric studies were carried out on the myocardial tissue. A linear increase in the myocardial volume occupied by the pigment was observed with advancing age. As a result of meclophenoxate treatment, a gradual decrease in the myocardial volume occupied by the pigment was noted. After 4-6 wk treatment, the pigment bodies were found lodged into the capillary endothelium and the lumen, facilitating the removal of the pigment via blood stream. Histochemical and micromorphometric analyses of ventricular myocardium of albino rats have shown th...
Impairments in oligodendrocyte development and resultant myelination deficits appear as a common ... more Impairments in oligodendrocyte development and resultant myelination deficits appear as a common denominator to all neurological diseases. An optimal in utero environment is obligatory for normal fetal brain development and later life brain functioning. Late embryonic and early postnatal brains from F1 rat born to protein malnourished mothers were studied through a combination of immunocytochemical and quantitative PCR assay for analyzing the relative expression of platelet-derived growth factor receptor-α (PDGFRα), myelin-associated glycoprotein (MAG), proteolipid protein (PLP), and myelin oligodendrocyte glycoprotein (MOG) to determine oligodendrocyte genesis, differentiation, maturation, and myelination. Myelin integrity and corpus callosum caliber was assessed by Luxol fast blue (LFB) staining, whereas grip strength test and open field activity monitoring for behavioral evaluation in F1 rats. We demonstrate that intra-generational protein deprivation results in drastically low PDGFRα+ oligodendrocyte precursor (OPC) population and significantly reduced expression of myelin protein genes resulting in poor pre-myelinating and mature myelinating oligodendrocyte number, hypo-myelination, and misaligned myelinated fibers. LFB staining and MOG immunolabeling precisely revealed long-term changes in corpus callosum (CC) caliber and demyelination lesions in LP brain supporting the behavioral and cognitive changes at early adolescence and adulthood following maternal protein malnutrition (PMN). Thus, intra-generational PMN negatively affects the oligodendrocyte development and maturation resulting in myelination impairments and associated with behavioral deficits typically mimicking clinical hallmarks of neuropsychiatric disorders. Our results further strengthen and augment the hypothesis “Impaired gliogenesis is a big hit for neuropsychiatric phenotype.”
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