Perivascular cells increase expression of ciliary neurotrophic factor following partial denervation of the rat neurohypophysis

Abstract

The expression of ciliary neurotrophic factor (CNTF) was investigated immunocytochemically during the axonal degeneration and collateral axonal sprouting response that follows partial denervation of the rat neurohypophysis. A significant increase in the number of CNTFimmunoreactive (CNTF-ir) cells was observed in the neurohypophysis of partially denervated animals compared to age-matched sham-operated controls by 5 days post-denervation, remaining elevated throughout the 30 day post denervation period. Stereometric assessment of the numbers of CNTF-ir cells within the partially denervated neurohypophysis demonstrated a 36% increase by 3 days following denervation reaching 130% of control values by 10 days post-lesion. The cell numbers remained elevated throughout the 30 days post-lesion period suggesting that CNTF may play a role in the neurosecretory axonal sprouting process known to occur between 10 and 30 days post-denervation. Subsequent preparations pairing anti-CNTF with antibodies against ED1, CR3, p75 low affinity neurotrophin receptor (p75 LNGFR ), and S100β, demonstrated that CNTF was exclusively localized in a phenotypically-distinct population of perivascular cells. The association of perivascular cells with phagocytic activity was confirmed by dual label fluorescence microscopy showing the colocalization of P75 LNGFR -ir and OX-42-ir in cells expressing the ED-1 antigen. No increase in CNTF-ir was observed in non-injured animals in which heightened levels of neurosecretory activity were induced physiologically. These results suggest that increased CNTF-ir occurs in response to conditions which induce high levels of phagocytic activity by perivascular cells in the axotomized neurohypophysis which is sustained throughout a period in which axonal sprouting is known to occur in the partially denervated neurohypophysis.

Effects of ciliary neurotrophic factor and leukemia inhibiting factor on oxytocin and vasopressin magnocellular neuron survival in rat and mouse hypothalamic organotypic cultures

“…Since the application of Bc1-XL and caspase inhibition was also found to increase the survival of the Oxt-and Avp-MCNs in the SON in organotypic culture (House et al, 2006) this lent further support for the proposal that the mechanism of axotomy-induced cell death was apoptosis (Vutskits et al, 1998). CNTF and the CNTF receptor have found to be present in the HNS system in vivo (Lo et al, 2008; Watt et al, 2006; Watt, et al, 2008) consistent with the view that this neurotrophic factor normally plays a role to sustain the MCNs in vivo .…”

Absence of axonal sprouting following unilateral lesion in 125‐day‐old rat supraoptic nucleus may be due to age‐dependent decrease in protein levels of ciliary neurotrophic factor receptor alpha

“…However, the precise role of CNTF in the NL is still not known. To this point, there is evidence indicating that CNTF‐immunoreactive cells of the NL are perivascular cells that may be neuronophagic during the axonal degeneration that follows partial denervation of the 35‐day‐old rat NL (Lo, SunRhodes, & Watt, ) suggesting that CNTF may play a role in axonal degeneration, as opposed to axonal sprouting in the NL.…”

Inhibition of the Jak-STAT pathway prevents CNTF-mediated survival of axotomized oxytocinergic magnocellular neurons in organotypic cultures of the rat supraoptic nucleus

“…We previously hypothesized that CNTF plays a role in the axonal reorganization of magnocellular neurons in the SON following injury (Askvig, et al, 2012, Lo, et al, 2008, Watt, et al, 2006, Watt, et al, 2009). In support of this hypothesis we demonstrated that following axotomy CNTF and the CNTF receptor components are increased in the SON both during the period of axonal sprouting and neuronal injury (Askvig, et al, 2012).…”