DOI: 10.1007/s12640-017-9720-2 Pages: 175-186
Article Type: ORIGINAL ARTICLE

Postnatal LPS Challenge Impacts Escape Learning and Expression of Plasticity Factors Mmp9 and Timp1 in Rats: Effects of Repeated Training

1. University Hospital of Würzburg, University of Würzburg, Section of Molecular Psychiatry, Clinical Research Unit of Disorders of Neurodevelopment and Cognition, Centre of Mental Health

2. Institute of Experimental Medicine, Laboratory of Neurobiology of the Brain Integrative Functions, I.P. Pavlov Department of Physiology

3. Institute of Physiologically Active Compounds, Russian Academy of Sciences, Laboratory of Biomolecular Screening

4. Maastricht University, Department of Neuroscience

5. I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, Laboratory of Molecular Mechanisms of Neuronal Interactions

6. I.M. Sechenov First Moscow State Medical University, Institute of Molecular Medicine, Laboratory of Psychiatric Neurobiology

7. I.M. Sechenov First Moscow State Medical University, Department of Normal Physiology

Correspondence to:
Tatyana Strekalova
Tel: 00 31 43 38 84 110
Email: t.strekalova@maastrichtuniversity.nl

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Abstract

Bacterial intoxication associated with inflammatory conditions during development can impair brain functions, in particular evolutionarily novel forms of memory, such as explicit learning. Little is known about the dangers of early-life inflammation on more basic forms of learning, for example, the acquisition of motor escape abilities, which are generally better preserved under pathological conditions. To address this limitation in knowledge, an inflammatory response was elicited in Wistar pups by lipopolysaccharide (LPS) injections (25 μg/kg) on postnatal days P15, P18 and P21. The acquisition of escape behaviour was tested from P77 by active avoidance footshock model and water maze. Open-field behaviour and blood corticosterone levels were also measured. Rat brain tissue was collected from pups 2 h post-injection and from adult rats which either underwent escape training on P77–P81 or remained untrained. mRNA levels of developmental brain plasticity factors MMP-9 and TIMP-1 were investigated in the medial prefrontal cortex and ventral/dorsal hippocampus. LPS-challenged rats displayed moderately deficient escape responses in both memory tests, increased freezing behaviour and, surprisingly, reduced blood cortisol levels. Mmp9 and Timp1, and their ratio to one another, were differentially altered in pups versus adult untrained rats but remained unchanged overall in rats trained in either learning task. Together, our data indicate that systemic pro-inflammatory response during early postnatal development has long-lasting effects, including on the acquisition of motor escape abilities and plasticity factor expression, into adulthood. Our data suggest that altered stress response could possibly mediate these deviations and repeated training might generate positive effects on plasticity under the employed conditions.

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  • Accepted: Mar 3, 2017
  • Online: Apr 18, 2017
  • Revised: Mar 1, 2017

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