Loss of Hippocampal Calretinin and Parvalbumin Interneurons in the 5XFAD Mouse Model of Alzheimer’s Disease

Abstract

The deposition of amyloid-β peptides in the form of extracellular plaques and neuronal degeneration belong to the hallmark features of Alzheimer’s disease (AD). In addition, impaired calcium homeostasis and altered levels in calcium-binding proteins seem to be associated with the disease process. In this study, calretinin- (CR) and parvalbumin- (PV) positive gamma-aminobutyric acid-producing (GABAergic) interneurons were quantified in different hippocampal subfields of 12-month-old wild-type mice, as well as in the transgenic AD mouse models 5XFAD and Tg4-42. While, in comparison with wild-type mice, CR-positive interneurons were mainly reduced in the CA1 and CA2/3 regions in plaque-bearing 5XFAD mice, PV-positive interneurons were reduced in all analyzed subfields including the dentate gyrus. No reduction in CR- and PV-positive interneuron numbers was detected in the non-plaque-forming Tg4-42 mouse, although this model has been previously demonstrated to harbor a massive loss of CA1 pyramidal neurons. These results provide information about hippocampal interneuron numbers in two relevant AD mouse models, suggesting that interneuron loss in this brain region may be related to extracellular amyloid burden.

Neuronal spreading and plaque induction of intracellular Aβ and its disruption of Aβ homeostasis

“…3 c). The neurons in CA1 stratum oriens are interneurons and early loss of interneurons has been described in AD and the 5XFAD mouse [ 8 ]. We noted that the induced plaque-like labeling in the stratum oriens represented smaller deposits of aggregated Aβ than typical larger amyloid plaques (Fig.…”

“…Reduced NeuN associated with preserved DAPI signal can be seen with neuron damage even without loss of neurons [ 11 ]. However, loss of interneurons in CA1 hippocampus layers is seen early in 5xFAD mice [ 8 ] and Aβ aggregation in CA1 interneurons was previously associated with early plaque formation in 5xFAD mice [ 3 ].…”

Alzheimer’s pathology causes impaired inhibitory connections and reactivation of spatial codes during spatial navigation

“…Recent studies have also revealed inhibitory interneuron dysfunction in AD mice. Several studies have shown the loss of PV + inhibitory interneurons in 5XFAD mice (Ali et al, 2019;Flanigan et al, 2014;Giesers and Wirths, 2020). Both hAPP mice and human patients with AD have lower levels of sodium channel Nav1.1 specifically in inhibitory interneurons.…”

Modulation of Long-Term Potentiation by Gamma Frequency Transcranial Alternating Current Stimulation in Transgenic Mouse Models of Alzheimer’s Disease

“…Moreover, Olivier et al showed that PV can modulate short-term neuroplasticity, which was maintained for up to a few minutes, unlike long-term neuroplasticity [ 48 ]. In various mouse models of AD, including the 5xFAD, the density of PV-positive neurons decreased in the hippocampus [ 49 , 50 ]. Hence, we conducted a Western blot analysis of PV to identify whether external gamma oscillation application affected the change in the level of PV; there were no statistically significant differences in the PV levels among the groups.…”