Biology subjects

Nag, T. C.

Publications and source records attributed to Nag, T. C..

4 recordsLinked to original sources

bioRxiv2025

Structural Validation of the Intermediate Leptomeningeal Layer in the Human Central Nervous System

Traditionally, the human central nervous system (CNS) is described as having three meningeal layers, from outer to inner: dura mater, arachnoid mater, and pia mater. The arachnoid and pia mater are called the leptomeninges, and the space between them is filled with cerebrospinal fluid (CSF). Using gross dissection, light microscopy, and ultrastructural analysis of fresh postmortem and cadaveric CNS specimens spanning fetal to adult ages (N=61), we demonstrate a fibrocellular intermediate leptomeningeal layer (ILL) from the cortex to the caudal end of the spinal cord. The ILL divides the subarachnoid space (SAS) into two distinct structural compartments, through which vessels and nerves pass. The ILL shows unique structural features, such as dips into the brains sulci and fissures, as a double-fold membrane that bears intra-layer trabeculae, carries vessels, and forms the perivascular sheath. Moreover, throughout the CNS, it appears to be a non-sieved barrier, characterized by the presence of tight and adherens junctions. ILL, predominantly in the spinal cord, contains macrophage-like cells, indicating its layer-specific immune properties. The ILL warrants recognition as a distinct human meningeal layer with potential barrier and immune functions. SignificanceO_ST_ABSAn Intermediate Leptomeningeal Layer encloses the Central Nervous System in HumansC_ST_ABSThe integrated analysis of our macroscopic, microscopic, and ultrastructural study provides robust support for an intermediate leptomeningeal layer (ILL) in the subarachnoid space (SAS) of the human central nervous system (CNS) along the entire neural axis. The ILL is a fibrocellular macroscopic structure, with restricted permeability, that divides the cerebrospinal fluid (CSF)-filled SAS into two distinct structural compartments. Uniquely, ILL revealed the presence of cells with macrophage-like properties, suggesting a possible role in immune surveillance. The ILL may redefine the established concept of protective coverings of CNS, CSF circulation dynamics, and the role of leptomeninges in health and disease, including drug delivery.

neuroscience↗

bioRxiv2022

Acute sleep deprivation induces synaptic remodeling at the soleus muscle neuromuscular junction in rats

Sleep is important for cognitive and physical performance. Sleep deprivation not only affects neural functions but also results in muscular fatigue. A good nights sleep reverses these functional derangements caused by sleep deprivation. The role of sleep in brain function has been extensively studied. However, its role in neuromuscular junction or skeletal muscle morphology is sparsely addressed although skeletal muscle atonia and suspended thermoregulation during rapid eye movement sleep possibly provides a conducive environment for the muscle to rest and repair; somewhat similar to slow-wave sleep for synaptic downscaling. In the present study, we have investigated the effect of 24 h sleep deprivation on the neuromuscular junction morphology and neurochemistry using electron microscopy and immunohistochemistry in the rat soleus muscle. Acute sleep deprivation altered synaptic ultra-structure viz. mitochondria, synaptic vesicle, synaptic proteins, basal lamina, and junctional folds needed for neuromuscular transmission. Further acute sleep deprivation showed the depletion of the neurotransmitter acetylcholine and the overactivity of its degrading enzyme acetylcholine esterase at the neuromuscular junction. The impact of sleep deprivation on synaptic homeostasis in the brain has been extensively reported recently. The present evidence from our studies shows new information on the role of sleep on neuromuscular junction homeostasis and its functioning. Statement of significanceSleep causes synaptic downscaling in the brain, and allows the brain to carry out various housekeeping functions. Here we have reported that the function of the sleep-wake cycle on the synaptic homeostasis extends beyond the brain. Acute sleep deprivation caused significant alteration at ultra and macrostructure of antigravity muscle and the neuromuscular junction along with adaptation to new fiber type in rats. These morpho-functional changes were well correlated with the biochemical assessment of the acetylcholine at the neuromuscular junction. These changes were partially recovered when the rats were allowed to recover from sleep deprivation. The findings suggest a new avenue for a sleep study; employing the neuromuscular junction for exploring the effect of sleep at energy and synaptic homeostasis levels.

neuroscience↗

bioRxiv2022

Cognitive dysfunction and anxiety resulted from synaptic downscaling, hippocampal atrophy and ventricular enlargement in i.c.v. streptozotocin injected male Wistar rats

Insulin-resistant brain state is proposed to be the early sign of Alzheimers disease(AD), which can be studied in intracerebroventricular streptozotocin (ICV-STZ) rodent model. ICV-STZ is reported to induce sporadic AD with the majority of the disease hallmarks as phenotype. On the other hand, Available experimental evidence has used varying doses of STZ (<1 to 3mg/kg) and studied its effect for different study durations, ranging from 14-270 days. Though these studies suggest 3mg/kg of ICV-STZ to be the optimum dose for progressive pathogenesis, the reason for such is elusive. Here we sought to investigate the mechanism of action of 3mg/kg ICV-STZ on cognitive and non-cognitive aspects at a follow-up interval of two weeks for two months. On 60th day, we examined layer thickness, cell density, ventricular volume, spine density, protein expression related to brain metabolism and mitochondrial function by histological examination. Findings suggest progressive loss of spatial, episodic, avoidance memory with increase in anxiety in a span of two month. Furthermore, hippocampal neurodegeneration, ventricular enlargement, diffused amyloid plaque deposition, loss of spine in dentate gyrus and imbalance in energy homeostasis was found on 60th day post injection. Interestingly, AD rats showed a uniform fraction of time spent in four quadrants of water maze with change in strategy when they were exposed to height. Our findings reveal that ICV-STZ injection at a dose of 3mg/kg can cause cognitive and neuropsychiatric abnormalities due to structural loss both at neuronal as well as synaptic level, which is tightly associated with change in neuronal metabolism.

neuroscience↗

bioRxiv2018

Localisation and hypersecretion of Nerve Growth Factor in breast Phyllodes tumours: evidence from a preliminary study

BackgroundThe pathophysiology of the breast phyllodes tumours is uncertain. Currently, wide surgical removal is the only available treatment option. The histopathological diagnosis of phyllodes tumours is often confused with that of fibroadenomas due to a striking histological resemblance; hence a distinctive biomarker for this tumour type is warranted.\n\nMaterial & MethodsFresh human breast tissue was obtained from surgically excised breast phyllodes and fibroadenoma tumours (test, 2 cases each), breast cancer (positive control, 2 cases) and normal breast tissue (negative control, 1 case). Immunohistochemistry was performed for the detection of nerve growth factor (NGF) on frozen sections of the test and control tissues fixed in 4% paraformaldehyde, using the indirect streptavidin-biotin-peroxidase complex method. Sandwich ELISA on tissue homogenates of the same test and control cases was also performed to validate the immunohistochemical findings.\n\nResultsA marked difference in NGF expression was detected in phyllodes tumours compared to fibroadenomas. The maximum NGF expression was observed in phyllodes tissue followed by cancer tissue, and the least expression in fibroadenomas (3-5 times less than in phyllodes; comparable with normal breast tissue).\n\nConclusionNGF is known for its growth inducing potential in breast cancer, but its secretion by a benign breast tumour is not known in literature. This study reports abundant NGF secretion by breast phyllodes, raising the possibility of its potential role in tumour pathogenesis and progression that can be exploited therapeutically in future. We also propose that NGF may be used as a distinct biomarker of phyllodes tumours, for differentiating them from fibroadenomas during histopathology.

cancer biology↗