Publications by authors named "Durairaj Ragu-Varman"

Autism spectrum disorder (ASD) is known as a group of neurodevelopmental conditions including stereotyped and repetitive behaviors, besides social and sensorimotor deficits. Anatomical and functional evidence indicates atypical maturation of the striatum. Astrocytes regulate the maturation and plasticity of synaptic circuits, and impaired calcium signaling is associated with repetitive behaviors and atypical social interaction.

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One of the primary reasons for complications and death worldwide are cardiovascular diseases (CVDs), with a death toll of approximately 18 million per year. CVDs include cardiomyopathy, hypertension, ischemic heart disease, coronary heart disease, myocardial infarction, heart attack, hearth failure, etc. Over 80% of the CVD mortality is recorded from lower and middle-income countries.

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Article Synopsis
  • Autism spectrum disorders (ASD) involve difficulties in social communication and interaction, with genetic and environmental factors like toxins and drugs linked to their development.
  • Research using a mouse model exposed to the drug valproic acid (VPA) during pregnancy showed changes in repetitive behaviors and cognitive performance related to brain areas responsible for motor skills and learning.
  • The study found that these behavioral changes corresponded with lower levels of proteins necessary for excitatory synapse formation, suggesting that prenatal exposure to VPA affects brain function and behavior associated with ASD.
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Aberrant dopamine (DA) signaling is implicated in schizophrenia, bipolar disorder (BPD), autism spectrum disorder (ASD), substance use disorder, and attention-deficit/hyperactivity disorder (ADHD). Treatment of these disorders remains inadequate, as exemplified by the therapeutic use of d-amphetamine and methylphenidate for the treatment of ADHD, agents with high abuse liability. In search for an improved and non-addictive therapeutic approach for the treatment of DA-linked disorders, we utilized a preclinical mouse model expressing the human DA transporter (DAT) coding variant DAT Val559, previously identified in individuals with ADHD, ASD, or BPD.

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Altered amine transporter function, phosphorylation, and association with interacting proteins are evident in animals with a history of psychostimulant exposure. Our previous studies have shown that the Thr258/Ser259 motif in the norepinephrine transporter (NET) is involved in amphetamine (AMPH)-mediated NET regulation and behavior. However, the neurobiological consequences of in vivo Thr258/Ser259-dependent NET regulation in an intact animal model are unclear.

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Background: Amphetamine (AMPH) and other psychostimulants act on the norepinephrine (NE) transporter (NET) and the dopamine (DA) transporter (DAT) and enhance NE and DA signaling. Both NET and DAT share anatomical and functional characteristics and are regulated similarly by psychostimulants and receptor-linked signaling pathways. We and others have demonstrated that NET and DAT are downregulated by AMPH and substance P/neurokinin-1 receptor (NK1R)-mediated protein kinase C pathway.

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Dynorphin (DYN) is an endogenous neurosecretory peptide which exerts its activity by binding to the family of G protein-coupled receptors, namely the kappa opioid receptor (KOR). Opioids are associated with pain, analgesia, and drug abuse, which play a central role in mood disorders with monoamine neurotransmitter interactions. Growing evidence demonstrates the cellular signaling cascades linked to KOR-mediated monoamine transporters regulation in cell models and native brain tissues.

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Dopamine (DA) transporter (DAT) is dynamically regulated by several protein kinases and the Thr53 phosphorylation of DAT (pT53-DAT) is documented in heterologous cell models and in rat brain. However, the role of endogenous pT53-DAT in living animals has never been addressed. Here we generated and studied the pT53-lacking DAT mouse model (DAT-Ala53) by CRISPR/Cas9 technology.

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Social defeat (SD) has been implicated in different modulatory effects of physiology and behaviour including learning and memory. We designed an experiment to test the functional role of monoamine oxidase (MAO) in regulation of synaptic transmission, synaptic plasticity and memory in goldfish Carassius auratus. To test this, individuals were divided into three groups: (i) control; (ii) social defeat (SD) group (individuals were subjected to social defeat for 10 min by Pseudotropheus demasoni) and (iii) SD + MAO inhibitor pre-treated group.

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Serotonin (5-HT) transporter (SERT) plays a crucial role in serotonergic transmission in the central nervous system, and any aberration causes serious mental illnesses. Nevertheless, the cellular mechanisms that regulate SERT function and trafficking are not entirely understood. Growing evidence suggests that several protein kinases act as modulators.

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Dehydration-Induced Anorexia (DIA) is a murine model that reproduces weight loss and avoidance of food, despite its availability. The prefrontal cortex (PFC) integrates sensory inputs and updates associative learning to promote (hunger) or inhibit (satiety) food-seeking behavior. In this study we tested if anorexia induces a pro-inflammatory environment associated with microglia in the medial prefrontal cortex (mPFC) and orbitofrontal cortex (OFC), specific subregions of the PFC involved in appetite.

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Reuptake and clearance of released serotonin (5-HT) are critical in serotonergic neurotransmission. Serotonin transporter (SERT) is mainly responsible for clearing the extracellular 5-HT. Controlled trafficking, phosphorylation, and protein stability have been attributed to robust SERT activity.

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Individual variation in the addiction liability of amphetamines has a heritable genetic component. We previously identified (heterogeneous nuclear ribonucleoprotein H1) as a quantitative trait gene underlying decreased methamphetamine-induced locomotor activity in mice. Here, we showed that mice (both females and males) with a heterozygous mutation in the first coding exon of (H1) showed reduced methamphetamine reinforcement and intake and dose-dependent changes in methamphetamine reward as measured via conditioned place preference.

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Anorexia by osmotic dehydration is an adaptive response to hypernatremia and hyperosmolaemia induced by ingestion of a hypertonic solution. Dehydration-induced anorexia (DIA) reproduces weight loss and avoidance of food, despite its availability. By using this model, we previously showed increased reactive astrocyte density in the rat dorsal hippocampus, suggesting a pro-inflammatory environment where microglia may play an important role.

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Anorexia nervosa is an eating disorder observed primarily in young women. The neurobiology of the disorder is unknown but recently magnetic resonance imaging showed a volume reduction of the hippocampus in anorexic patients. Dehydration-induced anorexia (DIA) is a murine model that mimics core features of this disorder, including severe weight loss due to voluntary reduction in food intake.

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Exposure to a predator elicits an innate fear response and mimics several behavioral disorders related to post-traumatic stress disorder (PTSD). The protective role of an enriched condition (EC) against psychogenic stressors in various animal models has been well documented. However, this condition has not been tested in field mice in the context of PTSD.

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The activity-dependent expression of immediate-early genes (IEGs) and microRNA (miR)-132 has been implicated in synaptic plasticity and the formation of long-term memory (LTM). In the present study, we show that olfactory training induces the expression of IEGs (EGR-1, C-fos, C-jun) and miR-132 at similar time scale in olfactory bulb (OB) of Cynopterus sphinx. We examined the role of miR-132 in the OB using antisense oligodeoxynucleotide (AS-ODN) and demonstrated that a local infusion of AS-ODN in the OB 2h prior to training impaired olfactory memory formation in C.

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Enriched environmental condition (EC) has been known to reduce anxiety. In this study, we examined whether an EC could enhance anxiolytic behavior in the Indian field mouse Mus booduga by down-regulating the expression of glucocorticoid receptor (GR) through microRNA-124a. Wild individuals were captured at agricultural field, and then housed at standard conditions (SC) for 7days.

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Environmental enrichment (EE) has an influential role in reducing behavioral reactivity to stress. We previously observed that EE reduces the anxiety-like behavior in the field mouse Mus booduga accompanied by a reduction in the expression of molecules involved in the stress pathway. In this study, we demonstrate the effect of different housing condition on regulation of micro-RNA-183-SC35-mediated splicing of acetylcholinesterase (AChE).

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Postsynaptic densities (PSDs) contain proteins that regulate synaptic transmission. We examined two important examples of these, calcium/calmodulin-dependent protein kinase II (CaMKII) and PSD-95, in regard to the functional role of early growth response gene-1 (egr-1) in regulation of olfactory learning in the greater short-nosed fruit bat Cynopterus sphinx (family Pteropodidae). To test whether activation of egr-1 in the olfactory bulb (OB) is required for olfactory memory of these bats, bilaterally canulated individuals were infused with antisense (AS) or non-sense (NS)-oligodeoxynucleotides (ODN) of egr-1, or with phosphate buffer saline (PBS), 2h before the olfactory training.

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To study variation of infestations by the bat fly Raymondia lobulata (Diptera: Streblidae) on the greater false vampire bat Megaderma lyra (Chiroptera: Megadermatidae), we captured individual bats at their day roost in the south of India and recorded their rate of infestation continuously for a year. All examined bats (n = 72 individuals, 202 captures) were infested with parasites (n = 3,008). However, the recorded intensity of infestation (range 1-33) was gender-related and statistically higher in females than in males (F(1, 200) = 304.

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