| First Author | Sawano E | Year | 2015 |
| Journal | J Neurochem | Volume | 135 |
| Issue | 2 | Pages | 287-300 |
| PubMed ID | 26250996 | Mgi Jnum | J:226027 |
| Mgi Id | MGI:5695682 | Doi | 10.1111/jnc.13274 |
| Citation | Sawano E, et al. (2015) Reduction in NPY-positive neurons and dysregulation of excitability in young senescence-accelerated mouse prone 8 (SAMP8) hippocampus precede the onset of cognitive impairment. J Neurochem 135(2):287-300 |
| abstractText | The senescence-accelerated mouse prone 8 (SAMP8) strain is considered a neurodegeneration model showing age-related cognitive deficits with little physical impairment. Young SAMP8 mice, however, exhibit signs of disturbances in development such as marked hyperactivity and reduced anxiety well before the onset of cognitive impairment. As the key enzyme in local regulation of thyroid hormone (TH) signaling, type 2 deiodinase, was significantly reduced in the SAMP8 hippocampus relative to that of the normally aging SAM-resistant 1 (SAMR1), we used these two strains to compare the development of the hippocampal GABAergic system, which is known to be strongly affected by hypothyroidism. Among GABAergic components, neuronal K(+) /Cl(-) co-transporter 2 was down-regulated in SAMP8 transiently at 2 weeks. Although distribution of total GABAergic neurons was similar in both strains, 22-30% reduction was observed in the neuropeptide Y (NPY)-positive subpopulation of GABAergic neurons in SAMP8. Electrophysiological studies on hippocampal slices obtained at 4 weeks revealed that epileptiform activity, induced by high-frequency stimulation, lasted four times longer in SAMP8 compared with SAMR1, indicating a dysregulation of excitability that may be linked to the behavioral abnormalities of young SAMP8 and to neurodegeneration later on in life. Local attenuation of TH signaling may thus impact the normal development of the GABAergic system. Senescence-accelerated mouse prone 8 (SAMP8) shows marked hyperactivity and reduced anxiety before the onset of cognitive impairment. Compared with the normally aging SAM-resistant 1 (SAMR1), NPY-positive subpopulation of GABAergic neurons was reduced by 22-30% in the young SAMP8 hippocampus, leading to longer lasting epileptiform activity after high frequency stimulation. Reduction in the TH-activating type 2 deiodinase is suggested as a cause of this GABAergic impairment. |
