Expression of thymosin beta4 mRNA by activated microglia in the denervated hippocampus

Abstract

Thymosin beta4 is a major actin-sequestering molecule. Here, we report a prominent upregulation of thymosin beta4 in the hippocampus following entorhinal deafferentation. Northern blotting displayed a transient increase of thymosin beta4 mRNA in the deafferented hippocampus by 1.8, 2.3, 1.3 and 1.1-fold of controls, respectively, at 1, 3, 7 and 15 days post-lesion. In-situ hybridization confirmed that the induction of thymosin beta4 mRNA specifically occurred in the entorhinally denervated zones of the hippocampus. The double labeling of in-situ hybridization for thymosin beta4 mRNA with isolectin B4 cytochemistry showed that isolectin B4-positive microglial cells are responsible for deafferentation-induced thymosin beta4 mRNA expression. The results suggest that thymosin beta4 may participate in the process of microglial activation, which is the earliest event in lesion-induced plasticity.

Neuroprotective and neurorestorative effects of thymosin β4 treatment initiated 6 hours after traumatic brain injury in rats

“…26,70 Tβ4 is also involved in lesion-induced neuroplasticity through upregulation of microglia. 15,47 The signaling pathways beyond actin sequestration remain largely unknown. Tβ4 lacks stable folded structure in aqueous solution and acquires specific folded structures only on binding to a partner protein; Tβ4 offers many possibilities for interaction with multiple partners.…”

Treatment of traumatic brain injury with thymosin β4 in rats

“…The peptide has been implicated in lymphocyte maturation, carcinogenesis, apoptosis, angiogenesis, blood coagulation, and wound healing25,53 The peptide is also involved in lesion-induced neuroplasticity through microglia upregulation and it participates in the growth of neuronal processes 35. Increased expression of Tβ 4 was found in the microglia in the entorhinally denervated zones of the hippocampus,17 suggesting that Tβ 4 may participate in the process of activated microglia, the earliest event of lesion-induced plasticity. Intracerebroventricular administration of Tβ 4 significantly reduced hippocampal neuronal loss induced by kainic acid 40.…”

Thymosin β4 Up-regulation of MicroRNA-146a Promotes Oligodendrocyte Differentiation and Suppression of the Toll-like Proinflammatory Pathway

“…The expression of T␤4 in the brain is increased with neurodegenerative disease, such as Huntington disease (36), as well as in various experimental conditions, such as brain ischemia (37,38), kainic acid-induced seizure (39), and hippocampal denervation (40). Intracerebroventricular administration of T␤4 (10 l of a 10 M solution twice a day over 5 days starting from the day of kainic acid injection) prevented kainic acid-induced hippocampal neuronal loss or neurotoxicity (41).…”