Cochlear ablation in mice lacking SHP-1 results in an extended period of cell death of anteroventral cochlear nucleus neurons.
Cochlear ablation results in the death of anteroventral cochlear nucleus (AVCN) neurons from birth to approximately postnatal day 14 (P14) in the murine brainstem. It is not known whether microglial activation contributes to AVCN neuronal death following deafferentation. In order to determine whether microglial activation helps to define the period of neuronal susceptibility within AVCN, we performed unilateral cochlear ablation on mice lacking the protein tyrosine phosphatase SHP-1 (me/me). These mice have been shown to have an exaggerated microglial response following ischemic injury. In the present study, the glial and neuronal response to deafferentation within AVCN was examined in wild-type and me/me mice at P5, P14, and P21. Lack of SHP-1 results in robust microglial but not astrocyte activation within the ablated P14 me/me AVCN. These mice also exhibit approximately 28% neuronal death at P14, a time when normal wild-type littermate controls show little cell death. Glial activation and neuronal loss at P5 and P21 were similar between the two phenotypes, suggesting a role of activated microglia in inducing neuronal death beyond P14 but not P21. These results indicate that activated microglia may participate in determining whether neurons in AVCN live or die following deafferentation.
Department of Biomedical and Pharmaceutical Sciences, School of Pharmacy and Allied Health Sciences, University of Montana, Missoula, 59812, USA.
Jie
J
Zhao
Diana I
DI
Lurie
D000344:Afferent Pathways; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000502:physiology; D001253:Astrocytes / Q000502:physiology; D016923:Cell Death; D003051:Cochlea / Q000294:innervation; D017626:Cochlear Nucleus / Q000502:physiology*; D003714:Denervation; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008817:Mice, Mutant Strains; D017628:Microglia / Q000502:physiology*; D009457:Neuroglia / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D010641:Phenotype; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000172:deficiency / Q000502:physiology*; D013997:Time Factors
D047908:Intracellular Signaling Peptides and Proteins; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C509248:Ptpn6 protein, mouse