Elsevier

Experimental Neurology

Volume 176, Issue 2, August 2002, Pages 377-389
Experimental Neurology

Regular Article
Effect of 192 IgG-Saporin on Circadian Activity Rhythms, Expression of P75 Neurotrophin Receptors, Calbindin-D28K, and Light-Induced Fos in the Suprachiasmatic Nucleus in Rats

https://doi.org/10.1006/exnr.2002.7969Get rights and content

Abstract

Photic entrainment of circadian rhythms in mammals is mediated through a direct retinal projection to the core region of the suprachiasmatic nucleus (SCN), the circadian clock. A proportion of this projection contains the low-affinity p75 neurotrophic receptor (p75NTR). Neonatal monosodium glutamate (MSG) treatment, which dramatically reduces p75NTR immunoreactivity in the SCN has no impact on photic entrainment. In order to clarify the contribution of p75NTR fibers in photic entrainment, targeted lesions of the p75NTR-immunoreactive SCN plexus were performed using intracerebroventricular (ICV) or intrahypothalamic injections of the immunotoxin 192 IgG-saporin (SAP) in rats. SAP treatment effectively abolished p75NTR immunoreactivity within the SCN core. ICV SAP treatment produced three different behavioral activity patterns: Animals became arrhythmic, displayed a shorter free-running period, or remained rhythmic following the lesion. Arrhythmic animals had large hypothalamic lesion which encompassed the entire SCN. In rhythmic rats, ICV-SAP significantly reduced immunostaining for calbindin-D28k (CaBP) in the SCN, and rats with shortened free-running periods had the lowest number of CaBP immunoreactive cells. ICV SAP also attenuated light-induced Fos expression in the SCN core. Despite lack of p75NTR and reduced CaBP and Fos expression in the SCN, SAP-treated rhythmic rats displayed normal photic entrainment. Intrahypothalamic SAP treatment reduced CaBP expression in the SCN but had no effect on light-induced Fos expression, free-running rhythms, or photic entrainment. The data show that p75NTR-immunoreactive elements in the SCN are not required for photic entrainment.

References (53)

  • S. Koh et al.

    Localization of nerve 2growth factor receptor messenger RNA and protein in the adult rat brain

    Exp. Neurol.

    (1989)
  • F.S. Lee et al.

    Activation of Trk neurotrophin receptor signaling by pituitary adenylate cyclase-activating polypeptides

    J. Biol. Chem.

    (2002)
  • F.Q. Liang et al.

    Expression of brain-derived neurotrophic factor and its cognate receptor, TrkB, in the rat suprachiasmatic nucleus

    Exp. Neurol.

    (1998)
  • F.Q. Liang et al.

    Circadian rhythm of brain-derived neurotrophic factor in the rat suprachiasmatic nucleus

    Neurosci. Lett.

    (1998)
  • J.D. Mikkelsen et al.

    Gating of retinal inputs through the suprachiasmatic nucleus: Role of excitatory neurotransmission

    Neurochem. Int.

    (1995)
  • M.M Moga

    Delayed loss of p75 neurotrophin receptor-immunoreactivity in the rat suprachiasmatic nucleus and intergeniculate leaflet after binocular enucleation

    Neurosci. Lett.

    (1998)
  • L.P Morin

    The circadian visual system

    Brain Res. Brain Res. Rev.

    (1994)
  • T. Perry et al.

    Behavioral, histological and immunocytochemical consequences following 192 IgG-saporin immunolesions of the basal forebrain cholinergic system

    Brain Res. Bull.

    (2001)
  • G.E. Pickard et al.

    The effect of neonatally administered monosodium glutamate (MSG) on the development of retinofugal projections and entrainment of circadian locomotor activity

    Behav. Neural. Biol.

    (1982)
  • H.D. Piggins et al.

    Phase-shifting effects of pituitary adenylate cyclase activating polypeptide on hamster wheel-running rhythms

    Neurosci. Lett.

    (2001)
  • K. Shinohara et al.

    Phase dependent response of vasoactive intestinal polypeptide to light and darkness in the suprachiasmatic nucleus

    Neurosci. Res.

    (1999)
  • R.G Wiley

    Neural lesioning with ribosome-inactivating proteins: Suicide transport and immunolesioning

    Trends Neurosci.

    (1992)
  • R.G Wiley

    Targeting toxins to neural antigens and receptors

    Semin. Cancer Biol.

    (1996)
  • M. Akiyama et al.

    Calcium and pituitary adenylate cyclase-activating polypeptide induced expression of circadian clock gene mPer1 in the mouse cerebellar granule cell culture

    J. Neurochem.

    (2001)
  • D.M. Berson et al.

    Phototransduction by retinal ganglion cells that set the circadian clock

    Science

    (2002)
  • M Bothwell

    Functional interactions of neurotrophins and neurotrophin receptors

    Annu. Rev. Neurosci.

    (1995)
  • Cited by (0)

    1

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