The majority of brain mast cells in B10.PL mice is present in the hippocampal formation

doi:10.1016/j.neulet.2005.09.029

Neuroscience Letters

Volume 392, Issue 3, 16 January 2006, Pages 174-177

https://doi.org/10.1016/j.neulet.2005.09.029 Get rights and content

Abstract

In the healthy mammalian CNS, mast cells (MCs) are thought to be located mostly in the thalamus. In this study, we have systematically assessed the presence of MCs in the hippocampal formation (HF) and in the thalamus of normal male and female B10.PL mice. Giemsa⁺ and Toluidine Blue⁺ MCs were detected by histomorphometric analyses at perivascular and intraparenchymal sites of both the hippocampus and the entorhinal cortex. We found a mean number of 4.4 MCs in the HF of female and 3.3 MCs in male B10.PL mice. In contrast to the HF, no MCs were present in the thalamus of these mice. Notably, all HF-MCs showed immunoreactivity for Kit, the receptor for the MC growth and maturation factor SCF, as assessed by FITC–avidin/Kit double labelling. We demonstrate that the majority of brain MCs is found in the hippocampus and entorhinal cortex of B10.PL mice, though the total number of MCs is small compared to other mouse strains or rats. The presence of most brain MCs in the HF of B10.PL mice suggests a potential role of MCs in hippocampal physiology and pathology.

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Acknowledgements

We thank Doreen Lüdecke and Nora Markgraf for excellent technical assistance and Kimberly Rosegger and Jodie Urcioli for critical reading of the manuscript. This work was supported in part by grants from the Deutsche Forschungsgemeinschaft (DFG) to Marcus Maurer and to Sven Hendrix (SFB507B11).

References (30)

L. Asarian et al.
Stimuli from conspecifics influence brain mast cell population in male rats
Horm. Behav.
(2002)
T. Brenner et al.
Mast cells in experimental allergic encephalomyelitis: characterization, distribution in the CNS and in vitro activation by myelin basic protein and neuropeptides
J. Neurol. Sci.
(1994)
F. Cirulli et al.
Increased number of mast cells in the central nervous system of adult male mice following chronic subordination stress
Brain Behav. Immunol.
(1998)
T. Kirino
Delayed neuronal death in the gerbil hippocampus following ischemia
Brain Res.
(1982)
L. Manni et al.
Neonatal handling in EAE-susceptible rats alters NGF levels and mast cell distribution in the brain
Int. J. Dev. Neurosci.
(1998)
R. Paus et al.
Mast cell involvement in murine hair growth
Dev. Biol.
(1994)
M. Sala et al.
Stress and hippocampal abnormalities in psychiatric disorders
Eur. Neuropsychopharmacol.
(2004)
U. Shanas et al.
Brain mast cells lack the c-kit receptor: immunocytochemical evidence
J. Neuroimmunol.
(1998)
O.B. Taiwo et al.
Unilateral spinal nerve ligation leads to an asymmetrical distribution of mast cells in the thalamus of female but not male mice
Pain
(2005)
T.C. Theoharides
Mast cells: the immune gate to the brain
Life Sci.
(1990)

M. Yang et al.

Morphological, immunohistochemical and quantitative studies of murine brain mast cells after mating

Brain Res.

(1999)

J.P. Zappulla et al.

Mast cells: new targets for multiple sclerosis therapy?

J. Neuroimmunol.

(2002)

X. Zhuang et al.

Mast cell number and maturation in the central nervous system: influence of tissue type, location and exposure to steroid hormones

Neuroscience

(1997)

X. Zhuang et al.

Reproductive behavior, endocrine state, and the distribution of GnRH-like immunoreactive mast cells in dove brain

Horm. Behav.

(1993)

D.G. Amaral et al.

Hippocampal formation

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¹: These two authors contributed equally to this study.

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The majority of brain mast cells in B10.PL mice is present in the hippocampal formation

Abstract

Section snippets

Acknowledgements

Horm. Behav.

J. Neurol. Sci.

Brain Behav. Immunol.

Brain Res.

Int. J. Dev. Neurosci.

Dev. Biol.

Eur. Neuropsychopharmacol.

J. Neuroimmunol.

Pain

Life Sci.

Brain Res.

J. Neuroimmunol.

Neuroscience

Horm. Behav.

Hippocampal formation