Neurotransmitters and neuromodulators involved in learning and memory

Learning and memory being highly specialized process of human brain involves complex interaction between neurotransmitters and cellular events. Over the years, the understandings of these processes have been evolving from psychological, neurophysiological, and pharmacological perspectives. The most widely appraised model of learning and memory involves attention, acquisition, storage and retrieval. Each of these events involve interplay of neurotransmitters such as dopamine, acetylcholine, norepinephrine, N-methyl-d-aspartic acid, gamma-aminobutyric acid, though preponderance of specific neurotransmitter have been documented. The formation of long-term memory involves cellular events with neuroplasticity. Further, dopamine is documented to play crucial role in the process of forgetting. Understanding of the processes of learning and memory not only facilitates drug discovery, but also helps to understand actions of several existing drugs. In addition, it would also help to enhance psychological interventions in children with learning disabilities. Thus, the review intends to summarize role of neurotransmitters and neuromodulators during different phases of learning and memory.

Neurosteroids: current perspective in therapy of neuropsychiatric disorders

Neurosteroids are natural or synthetic steroid derivatives which act locally in brain by modulating neuronal excitability. The objective of this study is to analyze available literature on classification, biosynthesis and mechanism of action, and therapeutic potential of neurosteroids. A review of literature pertaining to neurosteroids published from inception to 2018 was carried on data bases like PUBMED, Google Scholar and Science Direct. The search terms used were neurosteroids, neuro-active steroids, ganaxolone and GABA-A receptor modulators. Review of literature suggests neurosteroids are powerful neuro-modulators, involving rapid non-genomic and non-hormone receptor mechanisms. They are classified based on structure as pregnane, androstane and sulphated neurosteroids, and based on function as excitatory or inhibitory neurosteroids. They act via GABAA receptor (primarily), rho- GABA (?GABA), NMDA-glutamate and sigma receptor modulation. The inhibitory neurosteroids demonstrate sedative, anxiolytic and anticonvulsant actions, whereas the excitatory agents produce memory enhancing and anxiogenic effects. They show efficacy in various CNS and psychiatric conditions like epilepsy, anxiety, depression, learning and memory disorders and substance abuse. Endogenous neurosteroids have limited clinical use due to low bioavailability, lack of specificity and unwanted effects. Hence, synthetic agents like alphaxalone, ganaxolone, sepranolone and brexanolone which have better bioavailability and specificity, are being investigated in various phases of clinical trials. Neurosteroids are novel endogenous compounds with neuro-modulatory function and show promising effects in therapy of various neurological and psychiatric conditions. Further studies that prove their long term efficacy and safety may revolutionize the clinical approach to therapy of these conditions.

Diagnosis and Management of Functional Chest Pain in the Rome IV Era

Functional chest pain accounts for about a third of the patients with noncardiac chest pain. It is a very common functional esophageal disorder that remains even today a management challenge to the practicing physician. Based on the definition offered by the Rome IV criteria, diagnosis of functional chest pain requires a negative workup of noncardiac chest pain patients that includes, proton pump inhibitor test or empirical proton pump inhibitor trial, endoscopy with esophageal mucosal biopsies, reflux testing, and esophageal manometry. The mainstay of treatment are neuromodulators that are primarily composed of anti-depressants. Alternative medicine and psychological interventions may be provided alone or in combination with other therapeutic modalities.

Mapping and signaling of neural pathways involved in the regulation of hydromineral homeostasis

Several forebrain and brainstem neurochemical circuitries interact with peripheral neural and humoral signals to collaboratively maintain both the volume and osmolality of extracellular fluids. Although much progress has been made over the past decades in the understanding of complex mechanisms underlying neuroendocrine control of hydromineral homeostasis, several issues still remain to be clarified. The use of techniques such as molecular biology, neuronal tracing, electrophysiology, immunohistochemistry, and microinfusions has significantly improved our ability to identify neuronal phenotypes and their signals, including those related to neuron-glia interactions. Accordingly, neurons have been shown to produce and release a large number of chemical mediators (neurotransmitters, neurohormones and neuromodulators) into the interstitial space, which include not only classic neurotransmitters, such as acetylcholine, amines (noradrenaline, serotonin) and amino acids (glutamate, GABA), but also gaseous (nitric oxide, carbon monoxide and hydrogen sulfide) and lipid-derived (endocannabinoids) mediators. This efferent response, initiated within the neuronal environment, recruits several peripheral effectors, such as hormones (glucocorticoids, angiotensin II, estrogen), which in turn modulate central nervous system responsiveness to systemic challenges. Therefore, in this review, we shall evaluate in an integrated manner the physiological control of body fluid homeostasis from the molecular aspects to the systemic and integrated responses.