Distinct alterations in motor & reward seeking behavior are dependent on the gestational age of exposure to LPS-induced maternal immune activation.
The dopaminergic system is involved in motivation, reward and the associated motor activities. Mesodiencephalic dopaminergic neurons in the ventral tegmental area (VTA) regulate motivation and reward, whereas those in the substantia nigra (SN) are essential for motor control. Defective VTA dopaminergic transmission has been implicated in schizophrenia, drug addiction and depression whereas dopaminergic neurons in the SN are lost in Parkinson's disease. Maternal immune activation (MIA) leading to in utero inflammation has been proposed to be a risk factor for these disorders, yet it is unclear how this stimulus can lead to the diverse disturbances in dopaminergic-driven behaviors that emerge at different stages of life in affected offspring. Here we report that gestational age is a critical determinant of the subsequent alterations in dopaminergic-driven behavior in rat offspring exposed to lipopolysaccharide (LPS)-induced MIA. Behavioral analysis revealed that MIA on gestational day 16 but not gestational day 12 resulted in biphasic impairments in motor behavior. Specifically, motor impairments were evident in early life, which were resolved by adolescence, but subsequently re-emerged in adulthood. In contrast, reward seeking behaviors were altered in offspring exposed MIA on gestational day 12. These changes were not due to a loss of dopaminergic neurons per se in the postnatal period, suggesting that they reflect functional changes in dopaminergic systems. This highlights that gestational age may be a key determinant of how MIA leads to distinct alterations in dopaminergic-driven behavior across the lifespan of affected offspring.
Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; APC Microbiome Institute, University College Cork, Cork, Ireland; The Irish Centre for Fetal and Neonatal Translational Research (INFANT), Cork University Maternity Hospital, Cork, Ireland.
Megan E
ME
Straley
Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; APC Microbiome Institute, University College Cork, Cork, Ireland.
Wesley
W
Van Oeffelen
Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland.
Sarah
S
Theze
Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; APC Microbiome Institute, University College Cork, Cork, Ireland.
Aideen M
AM
Sullivan
Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; APC Microbiome Institute, University College Cork, Cork, Ireland.
Siobhain M
SM
O'Mahony
Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; APC Microbiome Institute, University College Cork, Cork, Ireland.
John F
JF
Cryan
Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; APC Microbiome Institute, University College Cork, Cork, Ireland; The Irish Centre for Fetal and Neonatal Translational Research (INFANT), Cork University Maternity Hospital, Cork, Ireland. Electronic address: g.okeeffe@ucc.ie.
Gerard W
GW
O'Keeffe
D000818:Animals; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000276:immunology / Q000502:physiology; D005260:Female; D005865:Gestational Age; D007249:Inflammation / Q000276:immunology; D008297:Male; D009043:Motor Activity / Q000276:immunology* / Q000502:physiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000276:immunology* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley / Q000276:immunology; D012201:Reward; D013378:Substantia Nigra / Q000276:immunology / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000276:immunology / Q000378:metabolism
D004298:Dopamine
Dopaminergic; Fetal programming; Lipopolysaccharide; Maternal immune activation; Midbrain; Motor behavior; Neuron; Offspring behavior; Parkinson’s disease; Reward behavior