A Moderate Increase of Physiological CO2 in a Critical Range during Stable NREM Sleep Episode: A Potential Gateway to REM Sleep

Sleep is characterized as rapid eye movement (REM) and non-rapid eye movement (NREM) sleep. Studies suggest that wake-related neurons in the basal forebrain, posterior hypothalamus and brainstem, and NREM sleep-related neurons in the anterior-hypothalamic area inhibit each other, thus alternating sleep–wakefulness. Similarly, pontine REM-ON and REM-OFF neurons reciprocally inhibit each other for REM sleep modulation. It has been proposed that inhibition of locus coeruleus (LC) REM-OFF neurons is pre-requisite for REM sleep genesis, but it remains ambiguous how REM-OFF neurons are hyperpolarized at REM sleep onset. The frequency of breathing pattern remains high during wake, slows down during NREM sleep but further escalates during REM sleep. As a result, brain CO2 level increases during NREM sleep, which may alter REM sleep manifestation. It has been reported that hypocapnia decreases REM sleep while hypercapnia increases REM sleep periods. The groups of brainstem chemosensory neurons, including those present in LC, sense the alteration in CO2 level and respond accordingly. For example, one group of LC neurons depolarize while other hyperpolarize during hypercapnia. In another group, hypercapnia initially depolarizes but later hyperpolarizes LC neurons. Besides chemosensory functions, LC REM-OFF neurons are an integral part of REM sleep executive machinery. We reason that increased CO2 level during a stable NREM sleep period may hyperpolarize LC neurons including REM-OFF, which may help initiate REM sleep. We propose that REM sleep might act as a sentinel to help maintain normal CO2 level for unperturbed sleep

Role of norepinephrine in the regulation of rapid eye movement sleep

Sleep and wakefulness are instinctive behaviours that are present across the animal species. Rapid eye movement (REM) sleep is a unique biological phenomenon expressed during sleep. It evolved about 300 million years ago and is noticed in the more evolved animal species. Although it has been objectively identified in its present characteristic form about half a century ago, the mechanics of how REM is generated, and what happens upon its loss are not known. Nevertheless, extensive research has shown that norepinephrine plays a crucial role in its regulation. The present knowledge that has been reviewed in this manuscript suggests that neurons in the brain stem are responsible for controlling this state and presence of excess norepinephrine in the brain does not allow its generation. Furthermore, REM sleep loss increases levels of norepinephrine in the brain that affects several factors including an increase in Na-K ATPase activity. It has been argued that such increased norepinephrine is ultimately responsible for REM sleep deprivation, associated disturbances in at least some of the physiological conditions leading to alteration in behavioural expression and settling into pathological conditions

The prevalence of sleep loss and sleep disorders in young and old adults

The ability to sleep declines with age. The National Sleep Foundation, USA has recommended a minimum sleep amount for all ages. Individuals who experience sleep lesser than the recommended amount could be sleep-deprived. Several factors like stress, altered circadian cycle, medical conditions, etc. cause sleep deficiency. Almost 50–60 % of elderly population suffer from sleep disorders such as sleep apnea, restless legs syndrome, REM sleep behavior disorder, etc. Chronic sleep deprivation may further lead to the development of diseases such as Alzheimer's and Parkinson's. This paper reviews the prevalence of sleep disorders and consequences of sleep loss in young and old adults

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Not AvailableThe study has been conducted in the mid Himalayas of Uttarakhand for the availability of water resources for domestic and irrigation usage. The study was conducted in four villages namely Deu, Dhoira, Jutaya and Nichiya of Kalsi block of Dehradun district. From each village, 25 respondents were interviewed for asking details about water resources. The respondents were asked about number of springs which have been dried for last 5 years, the causes for drying of natural resources, impact of spring drying on the livelihood of people and the means of overcoming water shortage, and Govt. Role in Village upliftment. From the results, it was found out that for last 5 years; about 4-5 springs have been dried up. The major causes of drying of natural water resources were reduced rainfall, hot weather and reduction in number of forest trees. The impacts of drying of natural resources were: more time is involved in water collection activity and unavailability of water for irrigation purposes. The means of overcoming water shortages were naularecharge and afforestation etc. The facilities provided by the Govt. Official as reported by the respondents were imparting training, agricultural related activities, loan related facilities and participation in self help group activities etc.Not Availabl

Neural mechanism of rapid eye movement sleep generation: Cessation of locus coeruleus neurons is a necessity

Two types of neurons are involved in the regulation of rapid eye movement (REM) sleep, the REM-ON and the REM-OFF neurons. As the name suggests, the REM-OFF neurons cease firing during REM sleep and they are norepinephrinergic. It has been shown that cessation of these neurons is a pre-requisite for the generation of REM sleep and GABA shuts them off. Further, if these neurons do not shut off, there is increased levels of norepinephrine in the brain and loss of REM sleep. The REM sleep deprivation induced increase in norepinephrine is responsible for mediating at least REM sleep loss induced increase in Na+-K+ ATPase activity, which is likely to be the primary factor for causing REM sleep deprivation induced effects

Not Available

Not AvailableThe study has been conducted in the mid Himalayas of Uttarakhand for the availability of water resources for domestic and irrigation usage. The study was conducted in four villages namely Deu, Dhoira, Jutaya and Nichiya of Kalsi block of Dehradun district. From each village, 25 respondents were interviewed for asking details about water resources. The respondents were asked about number of springs which have been dried for last 5 years, the causes for drying of natural resources, impact of spring drying on the livelihood of people and the means of overcoming water shortage, and Govt. Role in Village upliftment. From the results, it was found out that for last 5 years; about 4-5 springs have been dried up. The major causes of drying of natural water resources were reduced rainfall, hot weather and reduction in number of forest trees. The impacts of drying of natural resources were: more time is involved in water collection activity and unavailability of water for irrigation purposes. The means of overcoming water shortages were naula recharge and afforestation etc. The facilities provided by the Govt. Official as reported by the respondents were imparting training, agricultural related activities, loan related facilities and participation in self help group activities etc.Not Availabl

Increased turnover of Na-K ATPase molecules in rat brain after rapid eye movement sleep deprivation

It has been shown that rapid eye movement (REM) sleep deprivation increases Na-K ATPase activity. Based on kinetic study, it was proposed that increased activity was due to enhanced turnover of enzyme molecules. To test this, anti-α 1 Na-K ATPase monoclonal antibody (mAb 9A7) was used to label Na-K ATPase molecules. These labeled enzymes were quantified on neuronal membrane by two methods: histochemically on neurons in tissue sections from different brain areas, and by Western blot analysis in control and REM sleep-deprived rat brains. The specific enzyme activity was also estimated and found to be increased, as in previous studies. The results confirmed our hypothesis that after REM sleep deprivation, increased Na-K ATPase activity was at least partly due to increased turnover of Na-K ATPase molecules in the rat brain

Long term blocking of GABA-A receptor in locus coeruleus by bilateral microinfusion of picrotoxin reduced rapid eye movement sleep and increased brain Na-K ATPase activity in freely moving normally behaving Rats

Isolated studies showed that norepinephrinergic REM-OFF neurons are active throughout except during rapid eye movement (REM) sleep when they are inhibited possibly by GABA. Similarly, independent studies have also reported that during REM sleep deprivation those REM-OFF neurons continue firing, that there is increased norepinephrine (NE) in the brain and that increased levels of NE increases the Na-K ATPase activity in the brain. However, it was not known if all those changes were directly related to REM sleep deprivation, what could be the mechanism for such changes and their patho-physiological significance. To confirm the same, based on the reports, mostly from our group, it was hypothesised that GABA antagonist in the locus coeruleus (LC) should at least significantly reduce REM sleep and simultaneously increase Na-K ATPase activity in the brain. To confirm the proposed hypothesis, picrotoxin, a GABA-A receptor antagonist, was bilaterally microinjected every 6 h for 36 h into the LC of freely moving normally behaving rats and the effects on electrophysiological signals signifying sleep-wakefulness and on brain synaptosome Na-K ATPase activity were estimated. The microinjection was done with the help of a remote control pump without handling or disturbing the rats. The findings that REM sleep was significantly reduced and there was associated increase in Na-K ATPase activity confirmed our hypothesis. The results also support our modified (GABA-mediated) model of neural connections in the LC for the regulation of REM sleep. Also, this is probably the first report to simulate REM sleep deprivation using receptor antagonist

Enzymatic and biochemical properties of lens in age-related cataract versus diabetic cataract: A narrative review

Cataract is the leading cause of blindness worldwide. There is an increased incidence of cataract formation in the diabetic population due to several factors. Diabetes mellitus accelerates the development of cataract. Oxidative stress results in most of the diabetic complications including diabetic cataract. Oxidative stress leading to the expression of various enzymes has also been proven as crucial for cataractous changes in the lens in old age. A narrative review was undertaken to investigate the expression of different biochemical parameters as well as enzymes in diabetic and senile cataracts. Identification of these parameters is crucial for the prevention and treatment of blindness. Combinations of MeSH terms and key words were used to do literature search in PubMed. The search resulted 35 articles and among them, 13 were relevant to the topic and were included in synthesis of results. Seventeen different types of enzymes were identified in the senile and diabetic cataracts. Seven biochemical parameters were also identified. Alteration in biochemical parameters and expression of enzymes were comparable. Majority of the parameters were raised or altered in diabetic cataract compared to senile cataract