Abstract
BackgroundExposure to traffic-related air pollution (TRAP) during development and/or in adulthood has been associated in many human studies with both neurodevelopmental and neurodegenerative diseases, such as autism spectrum disorder (ASD) and Alzheimer’s disease (AD) or Parkinson’s disease (PD).MethodsIn the present study, C57BL/6 J mice were exposed to environmentally relevant levels (250+/−50 μg/m3) of diesel exhaust (DE) or filtered air (FA) during development (E0 to PND21). The expression of several transcription factors relevant for CNS development was assessed on PND3. To address possible mechanistic underpinnings of previously observed behavioral effects of DE exposure, adult neurogenesis in the hippocampus and laminar organization of neurons in the somatosensory cortex were analyzed on PND60. Results were analyzed separately for male and female mice.ResultsDevelopmental DE exposure caused a male-specific upregulation of Pax6, Tbr1, Tbr2, Sp1, and Creb1 on PND3. In contrast, in both males and females, Tbr2+ intermediate progenitor cells in the PND60 hippocampal dentate gyrus were decreased, as an indication of reduced adult neurogenesis. In the somatosensory region of the cerebral cortex, laminar distribution of Trb1, calbindin, and parvalbumin (but not of Ctip2 or Cux1) was altered by developmental DE exposure.ConclusionsThese results provide additional evidence to previous findings indicating the ability of developmental DE exposure to cause biochemical/molecular and behavioral alterations that may be involved in neurodevelopmental disorders such as ASD.
Highlights
Exposure to traffic-related air pollution (TRAP) during development and/or in adulthood has been associated in many human studies with both neurodevelopmental and neurodegenerative diseases, such as autism spectrum disorder (ASD) and Alzheimer’s disease (AD) or Parkinson’s disease (PD)
Developmental diesel exhaust (DE) exposure is associated with increased expression of the transcription factors paired box 6 (Pax6), T-box brain 2 (Tbr2), T-box brain 1 (Tbr1), Specificity protein 1 (Sp1), and cAMP-responsive element binding protein 1 (Creb1) on PND3 Levels of mRNA of transcription factors known to modulate neurogenesis and neuronal differentiation were measured by qRT-PCR in whole brains from PND3 male and female mice exposed to DE or filtered air (FA) from embryonic day 0 (E0) to PND3
Developmental DE exposure is associated with decreased adult neurogenesis The presence of T-box brain 2 (Tbr2) has been used as a marker for neurogenesis during Central nervous system (CNS) development and in the adult brain, as it is expressed by intermediate neuronal progenitors [28, 39]
Summary
Exposure to traffic-related air pollution (TRAP) during development and/or in adulthood has been associated in many human studies with both neurodevelopmental and neurodegenerative diseases, such as autism spectrum disorder (ASD) and Alzheimer’s disease (AD) or Parkinson’s disease (PD). Methods: In the present study, C57BL/6 J mice were exposed to environmentally relevant levels (250+/−50 μg/m3) of diesel exhaust (DE) or filtered air (FA) during development (E0 to PND21). In utero and early childhood exposure to traffic-related air pollution (TRAP) has been associated with neurodevelopmental diseases such as autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder, and obsessivecompulsive disorder ([4, 23, 30, 50, 59, 62, 67]), and with neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) ([7, 12–14, 24, 25, 43, 63];). Air pollution exposure has been shown to inhibit adult neurogenesis in mice. Environmental toxicants that disrupt the balance between self-renewal and differentiation of NSCs during development could affect the progression of both neurodevelopmental and neurodegenerative disorders
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
