GABAergic and glutamatergic cells in the inferior colliculus dynamically express the GABA(A)R gamma(1) subunit during aging
Age-related hearing loss; age-related-changes; amino-acids; auditory-cortex; binding; brain; fischer-344 rat; GABA(A) receptor; GABA(A)R gamma(1) subunit; GABAergic; Geriatrics & Gerontology; Glutamatergic; glutamic-acid decarboxylase; hearing-loss; Inferior colliculus; Neurons; Neurosciences & Neurology; primary; receptive-fields
Age-related hearing loss may result, in part, from declining levels of gamma-amino butyric acid (GABA) in the aging inferior colliculus (IC). An upregulation of the GABA(A)R gamma(1) subunit, which has been shown to increase sensitivity to GABA, occurs in the aging IC. We sought to determine whether the upregulation of the GABA(A)R gamma(1) subunit was specific to GABAergic or glutamatergic IC cells. We used immunohistochemistry for glutamic acid decarboxylase and the GABA(A)R gamma(1) subunit at 4 age groups in the IC of Fisher Brown Norway rats. The percentage of somas that expressed the gamma(1) subunit and the number of subunits on each soma were quantified. Our results show that GABAergic and glutamatergic IC cells increasingly expressed the gamma(1) subunit from young age until expression peaked during middle age. At old age (similar to 77% of life span), the number of GABA(A)R gamma(1) subunits per cell sharply decreased for both cell types. These results, along with previous studies, suggest inhibitory and excitatory IC circuits may express the GABA(A)R gamma(1) subunit in response to the age-related decline of available GABA. Published by Elsevier Inc.
Robinson L C; Barat O; Mellott J G
Neurobiology of Aging
2019
2019-08
<a href="http://doi.org/10.1016/j.neurobiolaging.2019.04.007" target="_blank" rel="noreferrer noopener">10.1016/j.neurobiolaging.2019.04.007</a>
GABAergic and glutamatergic cells in the inferior colliculus dynamically express the GABAAR γ1 subunit during aging
Age-related hearing loss; GABAA receptor; GABAAR γ1 subunit; GABAergic; Glutamatergic; Inferior colliculus
Age-related hearing loss may result, in part, from declining levels of γ-amino butyric acid (GABA) in the aging inferior colliculus (IC). An upregulation of the GABAAR γ1 subunit, which has been shown to increase sensitivity to GABA, occurs in the aging IC. We sought to determine whether the upregulation of the GABAAR γ1 subunit was specific to GABAergic or glutamatergic IC cells. We used immunohistochemistry for glutamic acid decarboxylase and the GABAAR γ1 subunit at 4 age groups in the IC of Fisher Brown Norway rats. The percentage of somas that expressed the γ1 subunit and the number of subunits on each soma were quantified. Our results show that GABAergic and glutamatergic IC cells increasingly expressed the γ1 subunit from young age until expression peaked during middle age. At old age (∼77% of life span), the number of GABAAR γ1 subunits per cell sharply decreased for both cell types. These results, along with previous studies, suggest inhibitory and excitatory IC circuits may express the GABAAR γ1 subunit in response to the age-related decline of available GABA.
Robinson Lauren C; Barat Oren; Mellott Jeffrey G
Neurobiology of Aging
2019
2019-08
<a href="http://doi.org/10.1016/j.neurobiolaging.2019.04.007" target="_blank" rel="noreferrer noopener">10.1016/j.neurobiolaging.2019.04.007</a>
Drug abuse and depression: possible models for geriatric anorexia.
Humans; Aged; Dopamine/physiology; Norepinephrine/physiology; Aging/metabolism/*physiology; Anorexia/etiology/*physiopathology; Corticotropin-Releasing Hormone/physiology; Depression/etiology/*physiopathology; Feeding and Eating Disorders/*physiopathology; Morphine/pharmacology; Substance-Related Disorders/complications/*physiopathology
The central biochemical pathology of anorexia and the natural aging of the brain is similar. Biochemical models for drug withdrawal and depression may also assist in understanding geriatric anorexia. Norepinephrine, corticotropin releasing factor and beta-endorphin may key neurotransmitters in all of these conditions.
Giannini A J
Neurobiology of aging
1988
1988-02
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/s0197-4580(88)80010-1" target="_blank" rel="noreferrer noopener">10.1016/s0197-4580(88)80010-1</a>
Alterations in neurotransmitter amino acid content in the aging rat striatum are subregion dependent.
Male; Animals; Rats; Aging/*metabolism; Amino Acids/*analysis; Neurotransmitter Agents/*analysis; Corpus Striatum/*analysis; Inbred F344
The topographical distribution of putative neurotransmitter amino acids in both
Donzanti B A; Ung A K
Neurobiology of aging
1990
1990-04
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/0197-4580(90)90050-a" target="_blank" rel="noreferrer noopener">10.1016/0197-4580(90)90050-a</a>
Evidence of Wnt/beta-catenin alterations in brain and bone of a tauopathy mouse model of Alzheimer's disease.
*Alzheimer's disease; *Beta catenin; *Bone mineral density; *Neurodegeneration; *Tauopathy; *Wnt proteins; *Wnt Signaling Pathway; Alzheimer Disease/*genetics/*metabolism; Animal; Animals; beta Catenin/metabolism; Bone and Bones/*metabolism; Bone Density; Bone Remodeling/genetics; Brain/*metabolism; Disease Models; Female; Gene Expression; Male; Mice; Osteogenesis/genetics; Osteoporosis/etiology/genetics; tau Proteins/*metabolism; Tauopathies/genetics/*metabolism; Wnt Proteins/metabolism
Low bone mineral density (BMD) is a significant comorbidity in Alzheimer's disease (AD) and may reflect systemic regulatory pathway dysfunction. Low BMD has been identified in several AD mouse models selective for amyloid-beta or tau pathology, but these deficits were attributed to diverse mechanisms. In this study, we identified common pathophysiological mechanisms accounting for bone loss and neurodegeneration in the htau mouse, a tauopathy model with an early low BMD phenotype. We investigated the Wnt/beta-catenin pathway-a cellular signaling cascade linked to both bone loss and neuropathology. We showed that low BMD persisted in male htau mice aged from 6 to 14 months, remaining significantly lower than tau-null and C57BL/6J controls. Osteogenic gene expression in female and male htau mice was markedly reduced from controls, indicating impaired bone remodeling. In both the bone and brain, htau mice showed alterations in Wnt/beta-catenin signaling genes suggestive of increased inhibition of this pathway. These findings implicate dysfunctional Wnt signaling as a potential target for addressing bone loss in AD.
Dengler-Crish Christine M; Ball Hope C; Lin Li; Novak Kimberly M; Cooper Lisa Noelle
Neurobiology of aging
2018
2018-07
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.neurobiolaging.2018.03.021" target="_blank" rel="noreferrer noopener">10.1016/j.neurobiolaging.2018.03.021</a>
Aged chimpanzees exhibit pathologic hallmarks of Alzheimer's disease.
*Alzheimer's disease; *Amyloid-beta protein; *Chimpanzee; *Neurofibrillary tangle; *Primate; *Tau; Aging/*metabolism/*pathology; Alzheimer Disease/*metabolism/*pathology; Amyloid beta-Peptides/metabolism; Animals; Brain/*metabolism/*pathology; Female; Humans; Male; Neurofibrillary Tangles/metabolism/pathology; Pan troglodytes; tau Proteins/metabolism
Alzheimer's disease (AD) is a uniquely human brain disorder characterized by the accumulation of amyloid-beta protein (Abeta) into extracellular plaques, neurofibrillary tangles (NFT) made from intracellular, abnormally phosphorylated tau, and selective neuronal loss. We analyzed a large group of aged chimpanzees (n = 20, age 37-62 years) for evidence of Abeta and tau lesions in brain regions affected by AD in humans. Abeta was observed in plaques and blood vessels, and tau lesions were found in the form of pretangles, NFT, and tau-immunoreactive neuritic clusters. Abeta deposition was higher in vessels than in plaques and correlated with increases in tau lesions, suggesting that amyloid build-up in the brain's microvasculature precedes plaque formation in chimpanzees. Age was correlated to greater volumes of Abeta plaques and vessels. Tangle pathology was observed in individuals that exhibited plaques and moderate or severe cerebral amyloid angiopathy, a condition in which amyloid accumulates in the brain's vasculature. Amyloid and tau pathology in aged chimpanzees suggests these AD lesions are not specific to the human brain.
Edler Melissa K; Sherwood Chet C; Meindl Richard S; Hopkins William D; Ely John J; Erwin Joseph M; Mufson Elliott J; Hof Patrick R; Raghanti Mary Ann
Neurobiology of aging
2017
2017-11
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.neurobiolaging.2017.07.006" target="_blank" rel="noreferrer noopener">10.1016/j.neurobiolaging.2017.07.006</a>
Effects of aging on spinal opioid-induced antinociception.
5)-; Aging/*physiology; Ala(2)-MePhe(4)-Gly(5)-; Analgesics; Animals; D-Penicillamine (2; delta/agonists; Dose-Response Relationship; Drug; Enkephalin; Enkephalins/administration & dosage/pharmacology; Hot Temperature; Inbred F344; Injections; Male; mu/agonists; Nociceptors/*drug effects; Opioid; Opioid/administration & dosage/*pharmacology; Pain Measurement/drug effects; Rats; Receptors; Spinal; Spinal Cord/*physiology
Initial experiments were conducted to determine whether or not the aging process alters the ability of young, mature, or aged male Fischer 344 rats (5- to 6-, 15- to 16-, and 25- to 26-months-old, respectively) to respond to thermal nociceptive stimuli. Using the tail-flick analgesiometric assay, 25- to 26-month-old rats responded significantly faster to the heat source than 15- to 16-month-old animals, but no significant differences were noted between the 5- to 6-month-old and aged rats. Another series of investigations compared the effects of aging on the spinal antinociceptive properties of the mu opioid agonist [D-Ala2,N-methyl-Phe4,Gly5-ol] enkephalin (DAMPGO) and the delta agonist [D-Pen2,D-Pen5] enkephalin (DPDPE). In these studies, young, mature, and aged rats were injected intrathecally (IT) with different doses of DAMPGO or DPDPE, and opioid-induced antinociception was tested on the tail-flick test. All three age groups responded to IT DAMPGO in a dose-dependent manner but, for the most part, higher spinal doses were required to produce significant elevations in tail-flick latency in the aged cohort of rats. The spinal analgesic effects of DPDPE also declined with advanced age. The aging process apparently alters the pain-inhibitory function of mu and delta opioid receptors in the rat spinal cord.
Crisp T; Stafinsky J L; Hoskins D L; Dayal B; Chinrock K M; Uram M
Neurobiology of aging
1994
1994-04
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/0197-4580(94)90108-2" target="_blank" rel="noreferrer noopener">10.1016/0197-4580(94)90108-2</a>