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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 55 records · Page 3
All sourcesNASA NTRSDOE OSTI
DOE OSTI2024

Estradiol associations with brain functional connectivity in postmenopausal women

Abstract Objective Previous studies have found that estrogens play a role in functional connectivity in the brain; however, little research has been done regarding how estradiol is associated with functional connectivity in postmenopausal women. The purpose of this study was to examine the relationship between estradiol and functional connectivity in postmenopausal women. Methods Structural and blood oxygenation level–dependent resting-state magnetic resonance imaging scans of 88 cognitively healthy postmenopausal individuals were obtained along with blood samples collected the same day as the magnetic resonance imaging to assess hormone levels. We generated connectivity values in CONN toolbox version 20.b, an SPM-based software. Results A regression analysis was run using estradiol level and regions of interest (ROI), including the hippocampus, parahippocampus, dorsolateral prefrontal cortex, and precuneus. Estradiol level was found to enhance parahippocampal gyrus anterior division left functional connectivity during ROI-to-ROI regression analysis. Estradiol enhanced functional connectivity between the parahippocampal gyrus anterior division left and the precuneus as well as the parahippocampal gyrus anterior division left and parahippocampal gyrus posterior division right. An exploratory analysis showed that years since the final menstrual period was related to enhanced connectivity between regions within the frontoparietal network. Conclusions These results illustrated the relationship between estradiol level and functional connectivity in postmenopausal women. They have implications for understanding how the functioning of the brain changes for individuals after menopause that may eventually lead to changes in cognition and behavior in older ages.

Obstetrics & Gynecology↗
DOE OSTI2023

Drug-Inducible Gene Therapy Effectively Reduces Spontaneous Seizures in Kindled Rats but Creates Off-Target Side Effects in Inhibitory Neurons

Over a third of patients with temporal lobe epilepsy (TLE) are not effectively treated with current anti-seizure drugs, spurring the development of gene therapies. The injection of adeno-associated viral vectors (AAV) into the brain has been shown to be a safe and viable approach. However, to date, AAV expression of therapeutic genes has not been regulated. Moreover, a common property of antiepileptic drugs is a narrow therapeutic window between seizure control and side effects. Therefore, a long-term goal is to develop drug-inducible gene therapies that can be regulated by clinically relevant drugs. In this study, a first-generation doxycycline-regulated gene therapy that delivered an engineered version of the leak potassium channel Kcnk2 (TREK-M) was injected into the hippocampus of male rats. Rats were electrically stimulated until kindled. EEG was monitored 24/7. Electrical kindling revealed an important side effect, as even low expression of TREK M in the absence of doxycycline was sufficient to cause rats to develop spontaneous recurring seizures. Treating the epileptic rats with doxycycline successfully reduced spontaneous seizures. Localization studies of infected neurons suggest seizures were caused by expression in GABAergic inhibitory neurons. In contrast, doxycycline increased the expression of TREK-M in excitatory neurons, thereby reducing seizures through net inhibition of firing. These studies demonstrate that drug-inducible gene therapies are effective in reducing spontaneous seizures and highlight the importance of testing for side effects with pro-epileptic stressors such as electrical kindling. These studies also show the importance of evaluating the location and spread of AAV-based gene therapies in preclinical studies.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Detection of Apparent Early Rabies Infection by LN34 Pan-Lyssavirus Real-Time RT-PCR Assay in Pennsylvania

The Pennsylvania Department of Health Bureau of Laboratories (PABOL) tested 6855 animal samples for rabies using both the direct fluorescent antibody test (DFA) and LN34 pan-lyssavirus reverse transcriptase quantitative PCR (RT-qPCR) during 2017–2019. Only two samples (0.03%) were initially DFA negative but positive by LN34 RT-qPCR. Both cases were confirmed positive upon re-testing at PABOL and confirmatory testing at the Centers for Disease Control and Prevention by LN34 RT-qPCR and DFA. Rabies virus sequences from one sample were distinct from all positive samples processed at PABOL within two weeks, ruling out cross-contamination. Levels of rabies virus antigen and RNA were low in all brain structures tested, but were higher in brain stem and rostral spinal cord than in cerebellum, hippocampus or cortex. Taken together, the low level of rabies virus combined with higher abundance in more caudal brain structures suggest early infection. These cases highlight the increased sensitivity and ease of interpretation of LN34 RT-qPCR for low positive cases.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1974

Correlation of the Hippocampal theta rhythm to changes in hypothalamic temperature

Warming and cooling the preoptic anterior hypothalamic area in awake, loosely restrained rabbits was found to evoke theta rhythm. This is consistent with previous studies indicating that theta rhythm is a nonspecific response evoked by stimulation of several sensory modalities. Several studies have correlated theta rhythm with alertness. A neural pathway involving the hypothalamus, the hippocampus, the septal area, and the reticular formation is proposed. Thus, a role of this pathway may be to alert the animal to changes in its body temperature.

Saleh, M. A.↗
NASA NTRS1974

Correlation of hippocampal theta rhythm with changes in cutaneous temperature

Investigation of the possibility that the hippocampus performs the function of alerting an animal to changes in cutaneous temperature, using unanesthetized, loosely restrained rabbits. The results indicate that the hippocampal theta rhythm, which appears to be evoked by changes in cutaneous temperature, can be related to a specific type of hyppocampal neuron which is, in turn, connected with other areas of the brain involved in temperature regulation.

Horowitz, J. M.↗
NASA NTRS1975

Neural models on temperature regulation for cold-stressed animals

The present review evaluates several assumptions common to a variety of current models for thermoregulation in cold-stressed animals. Three areas covered by the models are discussed: signals to and from the central nervous system (CNS), portions of the CNS involved, and the arrangement of neurons within networks. Assumptions in each of these categories are considered. The evaluation of the models is based on the experimental foundations of the assumptions. Regions of the nervous system concerned here include the hypothalamus, the skin, the spinal cord, the hippocampus, and the septal area of the brain.

Horowitz, J. M.↗
NASA NTRS1977

Origins of serotonin innervation of forebrain structures

The tryptophan hydroxylase activity and high-affinity uptake of (3H) serotonin ((3H)5-HT) were measured in five discrete brain regions of rats following lesions of the dorsal or median raphe nuclei. Dorsal raphe lesions reduced enzyme and uptake activity in the striatum only. Median raphe lesions reduced activities in the hippocampus, septal area, frontal cortex, and, to a lesser extent, in the hypothalamus. These data are consistent with the suggestion that the dorsal and median raphe nuclei are the origins of two separate ascending serotonergic systems - one innervating striatal structures and the other mesolimbic structures, predominantly. In addition, the data suggest that measurements of high-affinity uptake of (3H)5-HT may be a more reliable index of innervation than either 5-HT content or tryptophan hydroxylase activity.

Kellar, K. J.↗
NASA NTRS1982

Neurophysiological responses to stressful motion and anti-motion sickness drugs as mediated by the limbic system

Performance is characterized in terms of attention and memory, categorizing extrinsic mechanism mediated by ACTH, norepinephrine and dopamine, and intrinsic mechanisms as cholinergic. The cholinergic role in memory and performance was viewed from within the limbic system and related to volitional influences of frontal cortical afferents and behavioral responses of hypothalamic and reticular system efferents. The inhibitory influence of the hippocampus on the autonomic and hormonal responses mediated through the hypothalamus, pituitary, and brain stem are correlated with the actions of such anti-motion sickness drugs as scopolamine and amphetamine. These drugs appear to exert their effects on motion sickness symptomatology through diverse though synergistic neurochemical mechanisms involving the septohippocampal pathway and other limbic system structures. The particular impact of the limbic system on an animal's behavioral and hormonal responses to stress is influenced by ACTH, cortisol, scopolamine, and amphetamine.

Kohl, R. L.↗
NASA NTRS1983

Gravitational Study of the Central Nervous System

A series of experiments conducted at 1G are discussed with reference to the role of calcium ions in information processing by the central nervous system. A technique is described which allows thin sections of a mammalian hippocampus to be isolated while maintaining neural activity. Two experiments carried out in hypergravic fields are also addressed; one investigating altered stimulation in the auditory system, the other determining temperature regulation responses in hypergravic fields.

Horowitz, J. M.↗
NASA NTRS1985

Effects of weightlessness on neurotransmitter receptors in selected brain areas

The central nervous system receptor dynamics of rats exposed to 7 days of microgravity are studied. The receptor affinity and receptor number at the hippocampus, lateral frontal cortex, prefrontal cortex, corpus striatum, cerebellum and pons-medulla, and the Na(+)/K(+)ATPase activity are examined. The data reveal that there is no significant change in the receptor affinity and receptor number for the lateral frontal cortex, prefrontal cortex, cerebellum and pons-medulla; however, there is an increase from 81 + or - 11 to 120 + or 5 fmole/mg protein in the receptor number for hippocampal binding, and a decrease in receptor number for the striatum from 172 + or - 14 to 143 + or - 10 fmoles/mg protein. A 9 percent decrease in Mg-dependent Na(+)/K(+)ATPase activity is observed. It is detected that the terminal mechanism may be affected by exposure to microgravity.

Miller, J. D.↗
NASA NTRS1986

Long term effects of low doses of Fe-56 ions on the brain and retina of the mouse - Ultrastructural and behavioral studies

Eight-month-old male C57BL6 mice were exposed without anesthesia to whole-body irradiation in circular holders. The mice were tested for behavioral decrements after 0.5 and 50 rads of Fe particle irradiation at 6 and 12 months postirradiation to obtain long-term results. A standard maze was used, and the animals were timed for completion thereof. A string test also was administered to the mice, testing their ability to grasp and move along a string to safety. The results from animals exposed to 50 rads were significantly different from control results to p = less than 0.001 in both systems of testing. The hippocampus (believed to be the location of environmental interaction in the brain) and the retina were examined for ultrastructural changes. The ultrastructural changes were similar to those found in the Cosmos 782, 936, and Argon experiments. The mouse data indicate that iron particles were able to induce long-term changes in the central nervous system which led to behavioral impairment.

Philpott, Delbert E.↗
NASA NTRS2002

Neural Correlates of Birth: Labor Contractions Induce C-Fos Expression In Newborn Rat Brain

At birth, the newborn mammal must make rapid adaptations to the extrauterine environment to survive. We have previously shown that labor contractions augment the appearance of adaptive responses at birth, viz., postpartum breathing and the onset of suckling. Since neuronal activity has been shown to upregulate the activity of immediate early genes (IEGs) in the brain, we analyzed the neural distribution of c-Fos protein expression in newborn rats using immunohistochemistry. Previous studies have reported a burst of c-Fos mRNA expression in mouse and rat brain at birth however relationships to labor and delivery have not been examined. In the present study, we exposed near-term rat fetuses to elements of the vaginal birth process: 1) Simulated labor contractions. 2) Postpartum cooling (22 deg C). 3) Umbilical cord occlusion. and 4) Stroking to mimic postpartum licking by the dam. Cardinally delivered newborns (VG) were compared with those delivered by cesarean section following either prenatal exposure to compressions (C) [simulated labor contractions], or no compressions (NC) [no labor contractions]. Similar patterns of c-fos activation were observed throughout hypothalamic and thalamic nuclei, hippocampus and cerebral cortex in VG and C newborns that were not apparent in NC newborns. Our results indicate that labor contractions play a role in the induction of widespread neural activation in the newborn brain.

Ronca, A. E.↗
NASA NTRS1987

Thermal dependence of neural activity in the hamster hippocampal slice preparation

1. Neural activity was recorded in an in vitro hamster hippocampal slice preparation while the temperature of the Ringer's solution bathing in the slice was controlled at selected levels. 2. The amplitude of the population spike (action potentials from a group of pyramidal cells) was measured as bath temperature was lowered from 35 degrees C to temperatures where a response could not be evoked. 3. Plots of population spike amplitude versus temperature have bell-shaped curves. The population spikes increased in amplitude as temperature was lowered from 35 degrees C, reached a peak amplitude between 25 and 20 degrees C, and then decreased until a response could not be evoked when temperature was further lowered. 4. These in vitro results obtained in the slice preparation are related to in vivo hippocampal studies. Results are interpreted as consistent with the proposal reviewed here that neural activity in the hippocampus plays a role at specific stages of entrance into and arousal from hibernation.

Non-NASA Center↗