Enhanced optical pulse broadening in free-space optical links due to the radiative effects of atmospheric aerosols.

Propagation through turbulent media produces complex amplitude fluctuations and temporal spreading of narrow optical pulses. Light-absorbing aerosols present in the atmospheric transmission path will perturb the refractive index structure parameter (Cn2) through atmospheric heating. The consequent enhancement in broadening and attenuation of ultrashort (femtosecond) optical pulses has been calculated by combining multi-satellite observations, radiosonde profiles and computational radiative transfer. It is shown that narrower optical pulses are more vulnerable to aerosol-induced impairments while broader pulses are more resilient, notwithstanding three to four orders of enhanced optical scintillation.

Radiative effects of atmospheric aerosols on the average channel capacity of free-space optical communication systems.

Free-space optical (FSO) communication systems employ unguided light beams propagating through the atmosphere to carry a large volume of data. The reliability of such data transfer can be hampered by various atmospheric effects. Based on an analytical model of a differential phase-shift keying FSO system through exponentiated Weibull turbulence, we investigate the effectiveness of beam width optimization and improved beam alignment, along with aperture averaging on the average channel capacity. Our results show significant signal deterioration produced due to the aerosol-induced optical turbulence, which substantially shadows the performance gain achieved through beam width optimization. Strong aerosol-induced atmospheric heating and the consequent enhanced optical scintillations result in reduction of the channel capacity by as much as 50% of its value when these effects are not considered or negligible. FSO systems are more resilient to aerosol-induced optical turbulence when the normalized beam width is less, and the average channel capacity can be significantly improved by improved beam alignment. These variations are weakly dependent under poor transmitter-receiver alignment conditions. Furthermore, the receiver aperture has a strong control on the link performance. While FSO systems with higher magnitude of normalized beam width have improved performance under all aperture diameter conditions; for a given beam configuration, large aperture diameter ensures a significant improvement in the link performance due to reduction in effects of scintillations.

Performance of free-space optical communication systems: effect of aerosol-induced lower atmospheric warming.

We report the effect of aerosol-induced local atmospheric heating and the resulting changes in the lower atmospheric optical turbulence on the performance of Free-Space Optical (FSO) communication links. A closed form mathematical expression is derived to estimate the influence of aerosol-induced warming on the Bit Error Rate (BER) of a Binary Phase Shift Keying FSO communication link through Gamma-Gamma modeled turbulence. Our results demonstrate a strong impact, with the aerosol-induced turbulence taking a toll on the signal-to-noise ratio of ~20 dB for a BER of 10-9. Aerosol-induced warming produces significant variations in BER compared to the clear atmospheric conditions and can subdue the benefits of improved beam alignment.

Enriched environment prevents hypobaric hypoxia induced neurodegeneration and is independent of antioxidant signaling.

Hypobaric hypoxia (HH) induced neurodegeneration has been attributed to several factors including increased oxidative stress, glutamate excitotoxicity, decreased growth factors, apoptosis, etc. Though enriched environment (EE) has been known to have beneficial effects in various neurological disorders, its effect on HH mediated neurodegeneration remains to be studied. Therefore, the present study was conducted to explore the effect of EE on HH induced neurodegeneration. Male Sprague-Dawley rats were placed in enriched and standard conditions during exposure to HH (7 days) equivalent to an altitude of 25,000 ft. The effect of EE on oxidative stress markers, apoptosis, and corticosterone level in hippocampus was investigated. EE during exposure to HH was found to decrease neurodegeneration as evident from decreased caspase 3 expression and LDH leakage. However, no significant changes were observed in ROS, MDA, and antioxidant status of hippocampus. HH elevates corticosterone level and affected the diurnal corticoid rhythm which may contribute to neurodegeneration, whereas EE ameliorate this effect. Because of the association of neurotrophins and stress and/or corticosterone the BDNF and NGF levels were also examined and it was found that HH decreases their level but concurrent exposure to EE maintains their level. Moreover, inhibition of Tyrosine kinase receptor (Trk) with K252a nullifies the protective effect of EE, whereas Trk activation with agonist, amitriptyline showed protective effect similar to EE. Taken together, we conclude that EE has a potential to ameliorate HH mediated neuronal degeneration which may act through antioxidant independent pathway by modulation of neurotrophins.

Isradipine antagonizes hypobaric hypoxia induced CA1 damage and memory impairment: Complementary roles of L-type calcium channel and NMDA receptors.

Hypobaric hypoxia leads to cognitive dysfunctions due to increase in intracellular calcium through ion channels. The purpose of this study was to examine the temporal contribution of L-type calcium channels and N-methyl-D-aspartate receptors (NMDARs) in mediating neuronal death in male Sprague Dawley rats exposed to hypobaric hypoxia simulating an altitude of 25,000 ft for different durations. Decreasing exogenous calcium loads by blocking voltage-gated calcium influx with isradipine (2.5 mg kg(-1)), and its efficacy in providing neuroprotection and preventing memory impairment following hypoxic exposure was also investigated. Effect of isradipine on calcium-dependent enzymes mediating oxidative stress and apoptotic cell death was also studied. Blocking of L-type calcium channels with isradipine reduced hypoxia-induced activation of calcium dependent xanthine oxidases, monoamine oxidases, cytosolic phospholipase A(2) and cycloxygenases (COX-2) along with concomitant decrease in free radical generation and cytochrome c release. Increased expression of calpain and caspase 3 was also observed following exposure to hypobaric hypoxia along with augmented neurodegeneration and memory impairment which was adequately prevented by isradipine administration. Administration of isradipine during hypoxic exposure protected the hippocampal neurons following 3 and 7 days of exposure to hypobaric hypoxia along with improvement in spatial memory.

Hypoxia-induced deactivation of NGF-mediated ERK1/2 signaling in hippocampal cells: neuroprotection by acetyl-L-carnitine.

Cellular and molecular pathways underlying hypoxic neurotoxicity and cell death are multifaceted and complex. Although many potentially neuroprotective agents have been investigated, the protection conferred is often inadequate, resulting in their insufficient clinical utility. In light of the above, we investigated the therapeutic potential and mechanism of action of acetyl-L-carnitine (ALCAR) in protecting hippocampal neurons from hypoxia-induced neurotoxicity and cellular death. Results showed decreased viability of hippocampal cells when exposed to hypoxia (3% O(2)) for 48 hr along with concomitant membrane depolarization, adenosine triphosphate depletion, DNA fragmentation, accentuated free radical production, and lactate dehydrogenase activity. Pretreatment with ALCAR significantly attenuated hypoxia-induced cytotoxicity in a dose-dependent manner and improved cellular glutathione levels and cytochrome c oxidase activity compared with normoxic controls. Supplementation of ALCAR also prevented apoptosis by down-regulating caspase-3 levels, cytochrome c release, and p-Bcl-2 expression. A decrease in nerve growth factor (NGF) was observed in hypoxic stress despite increased phosphorylation of ERK1/2 (extracellular signal-related kinase) and its downstream effector, Elk-1. Supplementation of ALCAR, on the other hand, up-regulated NGF and tyrosine kinase A expression along with concomitant increase in ERK1/2 phosphorylation, thus enhancing cell survival. ALCAR therefore provides neuroprotection by stabilizing mitochondrial membrane, restoring the cholinergic transmission, and more importantly, it stimulates NGF receptors, thus triggering cell survival pathway via ERK phosphorylation. Therefore, ALCAR may be useful as an effective therapeutic agent for hypoxic stress and associated neurodegenerative diseases.

Ceftriaxone rescues hippocampal neurons from excitotoxicity and enhances memory retrieval in chronic hypobaric hypoxia.

Exposure to high altitude is known to cause impairment in cognitive functions in sojourners. The molecular events leading to this behavioral manifestation, however, still remain an enigma. The present study aims at exploring the nature of memory impairment occurring on chronic exposure to hypobaric hypoxia and the possible role of glutamate in mediating it. Increased ionotropic receptor stimulation by glutamate under hypobaric hypoxic conditions could lead to calcium mediated excitotoxic cell death resulting in impaired cognitive functions. Since glutamate is cleared from the synapse by the Glial Glutamate Transporter, upregulation of the transporter can be a good strategy in preventing excitotoxic cell death. Considering previous reports on upregulation of the expression of Glial Glutamate Transporter on ceftriaxone administration, the therapeutic potential of ceftriaxone in ameliorating hypobaric hypoxia induced memory impairment was investigated in male Sprague Dawley rats. Exposure to hypobaric hypoxia equivalent to an altitude of 7600 m for 14 days lead to oxidative stress, chromatin condensation and neuronal degeneration in the hippocampus. This was accompanied by delayed memory retrieval as evident from increased latency and pathlength in Morris Water Maze. Administration of ceftriaxone at a dose of 200 mg/kg for 7 days and 14 days during the exposure on the other hand improved the performance of rats in the water maze along with decreased oxidative stress and enhanced neuronal survival when compared to hypoxic group without drug administration. An increased expression of Glial Glutamate Transporter was also observed following drug administration indicating faster clearance of glutamate from the synapse. The present study not only brings to light the effect of longer duration of exposure to hypobaric hypoxia on the memory functions, but also indicates the pivotal role played by glutamate in mediating excitotoxic neuronal degeneration at high altitude. The therapeutic potential of ceftriaxone in providing neuroprotection in excitotoxic conditions by increasing Glial Glutamate Transporter expression and thereby enhancing glutamate uptake from the synapse has also been explored.

Hypobaric hypoxia induces dendritic plasticity in cortical and hippocampal pyramidal neurons in rat brain.

Hypobaric hypoxia (HH), a predisposing environmental condition at high altitude (HA) encountered by many mountaineers jeopardizes their normal physiology like motor coordination and cognitive functions. Our previous studies revealed that the HH induces oxidative stress and neurodegeneration, which is associated with spatial memory impairment in rats. However, the dendritic changes after exposure to different duration of HH remain largely unknown. The aim of the present study was to investigate the duration-dependent dendritic changes in CA1, CA3 and entorhinal cortex (EC) of hippocampus and layer II of prefrontal cortex (PFC) with spatial memory functions in rats on exposure to different duration of HH. The rats were exposed to simulated HA of 6100 m for 3, 7, 14 and 21 days and the spatial reference memory was investigated using Morris water maze (MWM) and the morphological alteration of CA1, CA3, EC and layer II of PFC were investigated. There was a significant decrease in dendritic arborization and spine number along with increased number of damaged neurons, after 3, 7 and 14 days of HH but after 21 days of HH exposure the structural recovery was noted in all the regions. There was impairment of spatial memory after 3 and 7 days of exposure, but slight improvement of spatial memory was noted after 14 and 21 days of exposure. Our studies suggested that HH induces dendritic plasticity of PFC and hippocampal pyramidal neurons of rat brain, which might be associated with improvement of spatial memory function after 21 days of HH exposure.

Cobalt supplementation promotes hypoxic tolerance and facilitates acclimatization to hypobaric hypoxia in rat brain.

In the present study, we report the molecular mechanisms of action by cobalt in facilitating acclimatization to hypobaric hypoxia using male Sprague-Dawley rats as the model system. We determined hypoxic gasping time and survival time as a measure to assess the degree of tolerance of animals to hypobaric hypoxia by exposing the animals to an altitude of 10,668 m. Oral administration of cobalt chloride (12.5 mg Co/kg body weight, BW, for 7 days) increased gasping time and hypoxic survival time by 3 to 4 times compared to the control animals. This could be attributed to an increased expression and the DNA binding activity of hypoxia inducible transcriptional factor (HIF-1alpha) and its regulated genes, that is, erythropoietin (EPO), vascular endothelial growth factor (VEGF), glucose transporter-1 (Glut-1), and nitric oxide synthase (NOS) levels. This in turn leads to better oxygenation, oxygen delivery, glucose transport, and maintenance of vascular tone, respectively, under oxygen-limited conditions. This was further confirmed by lower levels of lactate dehydrogenase (LDH) activity and lactate in the brain of cobalt + hypoxia group compared with animals exposed to hypoxia. Glucose levels also increased after cobalt supplementation. The findings of the study provide a basis for the possible use of cobalt for facilitating acclimatization to hypoxia and other conditions involving oxygen deprivation.

Differential temporal response of hippocampus, cortex and cerebellum to hypobaric hypoxia: a biochemical approach.

Hypobaric hypoxia is known to cause cognitive dysfunctions and memory impairment. The present study aimed at exploring the occurrence of oxidative stress in hypobaric hypoxia and the differential temporal response of the hippocampus, cerebellum following hypobaric hypoxia. Animals were divided into control, 3 days, 7 days and 14 days exposure groups and were exposed to an altitude of 25,000 ft. Our study revealed an increase in lactate dehydrogenase activity along with increase in free radical generation and lipid peroxidation. We also noted depletion in the antioxidants and decrease in glutathione reductase and superoxide dismutase activity. There was significant decrease in reduced glutathione levels in the exposure groups when compared to the control which was accompanied by a concomitant increase in oxidized glutathione levels. Increase in glutamate dehydrogenase activity was observed coinciding with the decrease in glutathione levels which was accompanied with an increase in expression of vesicular glutamate transporter. The hippocampus was found to be more vulnerable to hypobaric hypoxia-induced oxidative stress in comparison to the cortex and cerebellum. An interesting observation was the onset of acclimatization on prolonged exposure to hypobaric hypoxia for a period of 14 days. Hypobaric hypoxia was found to affect various regions of the brain differentially and the response of each region varied as a function of time.

Hypobaric hypoxia damages the hippocampal pyramidal neurons in the rat brain.

Hypobaric hypoxia (HH), a predisposing environmental condition at high altitude (HA), encountered by many mountaineers, jeopardizes their normal physiology like motor coordination and cognitive functions. A large body of evidence shows that HH has deleterious effect on cognitive functions. Among them the hippocampal dependent memory deficit is well known. However, our current understanding of the mechanistic details of cognitive deficits at HA remains largely unclear and hence limits a solution for this problem. Therefore, the present study was designed to investigate the temporal component of the hippocampal pyramidal neuron damage in the rat brain subjected to chronic HH exposure. Three groups (sham HH, 3 days HH and 7 days HH) of rats were exposed to simulated HH equivalent to 6100 m in an animal decompression chamber for 3 or 7 days. Later, the hippocampal (CA1 and CA3) neurons were analysed for the cell morphology, neurodegeneration and DNA fragmentation. The CA1 and CA3 neurons showed HH induced neuronal pyknosis, cell shrinkage, and consequent inter-cellular vacuolization in the CA1 and CA3 areas. In addition, the total neuron (intact) numbers and mean surface area were decreased. The number of dead neurons increased significantly following exposure to HH for 3 or 7 days. The neurodegenerative (Fluoro jade B) and apoptotic (TUNEL) markers were more positive in CA1 and CA3 neurons. The magnitude of morphological changes, neurodegeneration and apoptosis was enhanced in 7 days HH group than 3 days HH group. Our studies indicate that CA3 neurons are more vulnerable to HH than CA1 neurons, and that may destabilize the neural circuits in the hippocampus and thus cause memory dysfunction.

Acetyl-L-carnitine ameliorates hypobaric hypoxic impairment and spatial memory deficits in rats.

Inadequate oxygen availability at high altitude causes oxidative stress and generation of reactive oxygen species, which may lead to memory impairment. Hippocampus, which plays a key role in the learning and memory processes, is especially vulnerable to hypoxic damage. The present study was aimed at investigating the effect of acetyl-L-carnitine on spatial working and reference memory deficits along with oxidative and apoptotic damage, caused by hypobaric hypoxia in male Sprague Dawley rats. Rats were trained in Morris Water Maze for eight days after which they were submitted to chronic hypobaric hypoxia exposure at a simulated altitude of 6100 m for three days. Rats received daily acetyl-L-carnitine at a dosage of 75 mg/kg body weight orally during exposure. Subsequent to exposure, performance of the animals was tested in Morris Water Maze, which revealed working memory impairment that was significantly improved by acetyl-L-carnitine. However, there was no change in the reference memory after hypobaric hypoxia exposure. Following behavioral study animals were sacrificed and biomarkers of oxidative damage like free radical production, lactate dehydrogenase activity, lipid peroxidation, antioxidant status and expression of apoptotic [viz. caspase-3, Apoptosis activating factor (Apaf-1), bax, cytochrome c] and anti-apoptotic protein-Bcl-2 were studied in the hippocampus. There was a significant increase in oxidative stress along with increased expression of apoptotic proteins and NR1 subunit of glutamate receptor indicating occurrence of excitotoxicity in hypoxia exposed rats. These results suggested that supplementation with acetyl-L-carnitine improves spatial working memory deficits reduces oxidative stress and inhibits apoptotic cascade induced by hypoxia.

N-acetyl cysteine supplementation prevents impairment of spatial working memory functions in rats following exposure to hypobaric hypoxia.

Exposure to high altitude (HA), especially extreme altitude, is associated with impairment of cognitive functions including memory and increased oxidative stress. However, the underlying mechanisms involved are not well understood. It is hypothesized that HA induced oxidative stress may be one of the factors underlying hypoxia induced memory impairment. The aim of the present study was to investigate the effect of hypobaric hypoxia (HH) on spatial working and reference memory functions, oxidative stress markers in rats and effect of supplementation of N-acetyl cysteine (NAC). The rats were divided into four groups. Group I served as normoxic (n=6), Group II served as hypoxic (n=6), Group III as hypoxia group treated with NAC (n=6) and Group IV served as normoxic group treated with NAC (n=6). Group II & III were exposed to HH for 3 days equivalent to 6100 m and received oral NAC supplementation (750 mg/kg) daily. Rats from all the groups were trained in Morris Water Maze (MWM) task for 8 consecutive days. Spatial working and reference memory were tested immediately after the termination of HH and then the rats were sacrificed for estimation of oxidative stress markers in hippocampus. Rats displayed significant deficits in spatial working memory, and increased oxidative stress along with decrease in antioxidant status on hypoxic exposure. Supplementation with NAC in hypoxia-exposed group improved spatial memory performance, and decreased oxidative stress. These findings indicate that hypoxic exposure is associated with increased oxidative stress, which may have caused memory deficit in rats exposed to simulated HA.

Mechanism of tert-butylhydroperoxide induced cytotoxicity in U-937 macrophages by alteration of mitochondrial function and generation of ROS.

tert-Butylhydroperoxide has been reported to inhibit growth and induce apoptosis in number of cell types, but little is known about the molecular mechanism mediating these effects. In the present study, we determined the molecular pathways that lead to apoptosis after treatment of cells with t-BOOH. The cells were exposed to different concentrations of t-BOOH (100-750 microM) for 1-4 h and various parameters such as cytotoxicity, ROS (reactive oxygen species) generation, MMP (mitochondrial membrane potential), intracellular Ca++ levels and expression of various proteins involved in apoptosis were determined. Exposure of U-937 cells to t-BOOH induced cytotoxicity in a time dependent manner with about 50% toxicity at 400 microM t-BOOH in 4h. t-BOOH treatment resulted in a time dependent increase in reactive oxygen species levels, Ca++ influx and annexin V positive cells. There was a significant fall in MMP following exposure to t-BOOH with time. t-BOOH treatment of U-937 cells leads to apoptosis, which is accompanied by activation of caspase-3. The caspase-3 inhibitor (Ac-DEVD-CHO) inhibits the cytotoxicity induced by t-BOOH, indicating a direct link between caspase-3 activation and cell death. This activation of apoptosis is accompanied by release of cytochrome c, down regulation of anti-apoptotic protein Bcl-2 levels with concurrent increase in pro-apoptotic proteins Bax and Bad levels. These observations indicate that t-BOOH induces cell death in U-937 macrophages by apoptosis, which is mediated through mitochondrial pathway.

Hypobaric hypoxia induces oxidative stress in rat brain.

High altitude exposure results in decreased partial pressure of oxygen and an increased formation of reactive oxygen and nitrogen species (RONS), which causes oxidative damage to lipids, proteins and DNA. Exposure to high altitude appears to decrease the activity and effectiveness of antioxidant enzyme system. The antioxidant system is very less in brain tissue and is very much susceptible to hypoxic stress. The aim of the present study was to investigate the time dependent and region specific changes in cortex, hippocampus and striatum on oxidative stress markers on chronic exposure to hypobaric hypoxia. The rats were exposed to simulated high altitude equivalent to 6100 m in animal decompression chamber for 3 and 7 days. Results indicate an increase in oxidative stress as seen by increase in free radical production, nitric oxide level, lipid peroxidation and lactate dehydrogenase levels. The magnitude of increase in oxidative stress was more in 7 days exposure group as compared to 3 days exposure group. The antioxidant defence system such as reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD) and reduced/oxidized glutathione (GSH/GSSG) levels were significantly decreased in all the three regions. The observation suggests that the hippocampus is more susceptible to hypoxia than the cortex and striatum. It may be concluded that hypoxia differentially affects the antioxidant status in the cortex, hippocampus and striatum.

Quercetin protects C6 glial cells from oxidative stress induced by tertiary-butylhydroperoxide.

The anti-oxidant and cyto-protective activity of quercetin against tertiary-butylhydroperoxide (t-BOOH) induced oxidative stress on C6 glial cells is reported. Exposure of the cells to t-BOOH resulted in a significant increase in cytotoxicity, reactive oxygen species (ROS) generation and lipid peroxidation. There was a significant increase in DNA strand breaks and fall in reduced GSH levels in cells exposed to t-BOOH. A significant increase in calcium ion influx was noticed in cells exposed to t-BOOH. Pre-treatment of cells with quercetin, vitamin C (vit C), Trolox, and deferoxamine (DFO) significantly inhibited t-BOOH induced cytotoxicity and ROS generation. Pretreatment of cells with quercetin, Trolox and DFO inhibited the DNA damage, maintained higher GSH levels and prevented calcium influx significantly. Although vit C protected the cells from cytotoxicity induced by t-BOOH, the intracellular Ca(2+) levels were significantly higher than the control cells. However, anti-oxidants like butylated hydroxy toluene (BHT), vitamin E (vit E), N-acetyl cysteine (NAC) did not have significant cytoprotection against t-BOOH induced oxidative injury in C6 glial cells.

Flavonoids protect U-937 macrophages against tert-butylhydroperoxide induced oxidative injury.

The study was carried out to determine the relative efficacies of polyphenolic flavonoids, quercetin, catechin and epicatechin against tert-BOOH induced oxidative stress in human macrophage, U-937 cell line. Exposure of the cells to tert-BOOH oxidative stress resulted in a significant increase in cytotoxicity and reactive oxygen species (ROS) generation. Further, a significant decrease in mitochondrial membrane potential and increase in lipid peroxidation and DNA damage was observed in cells exposed to tert-BOOH. Pretreatment of cells with quercetin, catechin and epicatechin significantly inhibited tert-BOOH induced cytotoxicity by inhibiting ROS generation. The flavonoids inhibited DNA damage induced by tert-BOOH and preserved the mitochondrial transmembrane potential significantly. Epicatechin and catechin were found to be more efficient than quercetin in inhibiting tert-BOOH induced cellular damage.

Neuroprotective effect of N-acetyl cysteine on hypoxia-induced oxidative stress in primary hippocampal culture.

Hippocampus has received a considerable attention in the recent past due to its role in a number of important functions such as learning and memory. The effect of hypoxia on neuronal cell injury especially on hippocampal cells is not well known. The aim of the present study was to characterize the biochemical changes in primary cultured hippocampal neurons during hypoxic exposure and the protective effect of N-acetyl cysteine on hypoxia-induced cytotoxicity. The hippocampal culture grown in 24-well plates was exposed to hypoxia for 3 h in a dessicator in 95% N(2), 5% CO(2) atmosphere at 37 degrees C. Later, the cells were allowed to recover for 1 h under normoxia. It was observed that there is an appreciable increase in cytotoxicity in cells exposed to hypoxia. Further, there was a significant decrease in mitochondrial membrane potential and appreciable increase in reactive oxygen species and single-strand DNA breaks in cells exposed to hypoxia compared to control. There is a significant fall in glutathione peroxidase, glutathione reductase, reduced glutathione levels, and nitric oxide in the cells exposed to hypoxia. Significant elevation in the intracellular calcium level in the cells on exposure to hypoxia was observed. Supplementation with NAC (50 microM) resulted in a significant cytoprotection, fall in ROS generation, and higher antioxidant levels similar to that of control cells. NAC also inhibited DNA strand breaks induced by hypoxia. The study indicates that NAC has significant neuroprotective activity during hypoxia in primary hippocampal culture.

Molecular regulation of dendritic spine dynamics and their potential impact on synaptic plasticity and neurological diseases.

The structure and dynamics of dendritic spines reflect the strength of synapses, which are severely affected in different brain diseases. Therefore, understanding the ultra-structure, molecular signaling mechanism(s) regulating dendritic spine dynamics is crucial. Although, since last century, dynamics of spine have been explored by several investigators in different neurological diseases, but despite countless efforts, a comprehensive understanding of the fundamental etiology and molecular signaling pathways involved in spine pathology is lacking. The purpose of this review is to provide a contextual framework of our current understanding of the molecular mechanisms of dendritic spine signaling, as well as their potential impact on different neurodegenerative and psychiatric diseases, as a format for highlighting some commonalities in function, as well as providing a format for new insights and perspectives into this critical area of research. Additionally, the potential strategies to restore spine structure-function in different diseases are also pointed out. Overall, these informations should help researchers to design new drugs to restore the structure-function of dendritic spine, a "hot site" of synaptic plasticity.