Table 1.

Exercise and neurological disorders across humans and animal model studies, with focus on the hippocampus

Disease	Humans	Animals	Hippocampus	References
Alzheimer’s disease	↑ Global cognition	↑ Learning and memory ↓ Anxiety ↑ Sensorimotor function ↑ Exploratory behavior	↓ Aβ load, APP ↓ or ↔Tau AT 100 epitope ↓ IL-1β, TNF-α ↑ LTP ↑ Neurogenesis	Heyn et al. 2004; Adlard et al. 2005; Lautenschlager et al. 2008; Baker et al. 2010; Belarbi et al. 2011; Garcia-Mesa et al. 2011; Liu et al. 2011; Rodríguez et al. 2011; Marlatt et al. 2013; Zhao et al. 2015
Anxiety	↓ State anxiety ↑ Sleep quality	↓ Anxiety-like behaviors ↓ Fear relapse ↓ Corticosterone response ↓ Social avoidance behavior ↓ Learning impairments ↓ Sympathetic nervous system activation Improved diurnal rhythms	↑ Glucocorticoid receptors ↑ BDNF ↑ Inhibitory interneuron mechanisms (ventral hippocampus) ↓ Melanin-concentrating hormone ↓ Serotonin responsiveness to stressors	Oldridge et al. 1991, 1995; Dishman 1997; Broocks et al. 1998; Russo-Neustadt et al. 1999; Bandelow et al. 2000; Greenwood et al. 2003, 2008, 2013; Fulk et al. 2004; Broman-Fulks and Storey 2008; Smits et al. 2008; Carmeli et al. 2009; Wedekind et al. 2010; Herring et al. 2011, 2015; Goldin et al. 2012; Jazaieri et al. 2012; Goldin et al. 2013; Hovland et al. 2013; Schoenfeld et al. 2013; Patki et al. 2014; Mika et al. 2015; Otsuka et al. 2015; Pan-Vazquez et al. 2015; Kim and Han 2016
Autism	↓ Stereotypic behavior ↑ Cognition and attention ↑ or ↔ Social–emotional functioning	↓ Aggressive tendencies ↑ Spatial learning ↑ Motor coordination and balance	↑ Neurogenesis ↑ Reelin ↑ BDNF ↑ LTP	Kern et al. 1982; Levinson and Reid 1993; Rosenthal-Malek and Mitchell 1997; Prupas and Reid 2001; Bass et al. 2009; Pan 2010; Nicholson et al. 2011; Oriel et al. 2011; Rosenblatt et al. 2011; Bahrami et al. 2012; Gabriels et al. 2012; Kim et al. 2013; Movahedi et al. 2013; Seo et al. 2013; Ward et al. 2013
Alcoholism	↓ Drinking days and heavy drinking days ↑ Days abstinent ↓ and ↔ Depression, anxiety, and abstinence self-efficacy ↓ Blood cortisol and ACTH compared with controls	↓ Alcohol preference and consumption ↓ Alcohol withdrawal score ↓ Blood cortisol	↑ BDNF ↑ Neurogenesis	Sinyor et al. 1982; Crews et al. 2004; Vedamurthachar et al. 2006; Coiro et al. 2007; Brown et al. 2009, 2014b; Ehringer et al. 2009; Klintsova et al. 2012; Motaghinejad et al. 2014, 2015; Gallego et al. 2015
Dementia	↑ Balance ↓ Agitation/aggression/disinhibition ↓ Apathy ↑ or ↔ Cognitive function ↑ Ability to perform activities of daily living ↓ or ↔ Depressive symptoms	↓ Cognitive impairment	↑ Neurogenesis ↑ BDNF	Van de Winckel et al. 2004; Christofoletti et al. 2008; Eggermont et al. 2009a,b; Conradsson et al. 2010; Hwang and Choi 2010; Kemoun et al. 2010; Venturelli et al. 2011; Volkers and Scherder 2011; Forbes et al. 2015; Telenius et al. 2015a,b; Choi et al. 2016
Depression	↓ Depression symptoms ↑ Coping strategies ↑ Episodic memory	↓ Depressive symptoms (↓ immobility time in forced swim test; ↑ sucrose preference)	↓ Toll-like receptor 4 ↓ IL-1β and IL-18 ↑ Neurogenesis ↑ VEGF, BDNF ↔ 5-HT ↑ Noradrenaline	Craft and Landers 1998; Stathopoulou et al. 2006; Daley 2008; Foley et al. 2008; Rethorst et al. 2009; De Zeeuw et al. 2010; Forsman et al. 2011; Krogh et al. 2011; Kiuchi et al. 2012; Cooney et al. 2013; Danielsson et al. 2013; Lee et al. 2013; Silveira et al. 2013; Josefsson et al. 2014; Lu et al. 2014; Sadeghi et al. 2016a,b
Epilepsy	↑ Seizure threshold ↓ or ↔ Seizure frequency ↓ EEG epileptiform discharges ↓ Seizures during mental and physical activity ↓ Comorbidities (depression, anxiety) ↑ Vigilance and attention	↓ Seizure frequency ↓ Seizure intensity ↓ Susceptibility to kindling and chemically induced seizures	↑ PV+ interneurons ↓ CA1 hyper-responsiveness ↑ LTP	Gotze et al. 1967; Nakken et al. 1990; Eriksen et al. 1994; Arida et al. 1999; McAuley et al. 2001; Heise et al. 2002; Arida et al. 2004, 2007, 2008, 2009, 2010; Rambo et al. 2009; Reiss et al. 2009; Tutkun et al. 2010; Eom et al. 2016
Huntington’s disease	∼↑ Motor function (gait speed and balance) and coordination ↑ Cognitive measures	↑ Corticostriatal connectivity ↑ or ↓ Gait function and motor coordination ↑ or ↓ Cognitive dysfunction Delays circadian dysfunction	↓ Neurogenesis	Pang et al. 2006; van Dellen et al. 2008; Cepeda et al. 2010; Potter et al. 2010; Renoir et al. 2012; Busse et al. 2013; Harrison et al. 2013; Khalil et al. 2013; Kloos et al. 2013
Multiple sclerosis	↔ or Moderately ↓ relapse rates ↔ Markers of immune function ↓ Physical disability progression ↓ MRI brain lesion volumes ↑ Neuroperformance (walking speed and endurance)	Delay disease onset ↓ Demyelination ↓ Duration of relapse ↓ Physical disability ↔ or ↓ Inflammatory response ↓ Dendritic spine loss ↓ Synaptic deficits ↑ NGF, BDNF ↓ Pain hypersensitivity ↓ Oxidative stress		Le Page et al. 1994, 1996; Motl and Snook 2008; Motl et al. 2008; Rossi et al. 2009; Motl and Pilutti 2012; Patel and White 2013; Benson et al. 2015; Pryor et al. 2015; Alvarez-Saavedra et al. 2016; Souza et al. 2016
Parkinson’s disease	↑ Motor function (gait, balance, strength) Improved mood ↓ or ↔ Depressive symptoms ↑ Spatial and verbal working memory ↑ Attention and processing speed ↓ Sleep disturbance (insomnia + daytime sleepiness)	↓ Spatial learning deficits ↔ Spatial memory ↑ Motor function	↑ Neurogenesis	Cruise et al. 2011; Shulman et al. 2013; Tomlinson et al. 2013; Nascimento et al. 2014; Park 2014; Uc et al. 2014; Canning et al. 2015; Dashtipour et al. 2015; David et al. 2015; Klein et al. 2016
Posttraumatic stress disorder (PTSD)	↓ PTSD symptoms ↓ Depressive symptoms	↓ Acoustic startle response ↑ Stress resilience ↑ Elevated plus maze activity ↑ Spatial learning ↓ Plasma corticosterone ↓ Depressive-like behavior ↓ Anxiety-like behavior	↑ BDNF ↑ Neuropeptide Y ↑ Phosphorylated δ-opioid receptor ↑ Neurogenesis	Kim and Seo 2013; Mitchell et al. 2014; Patki et al. 2014; Van Der Kolk et al. 2014; Hoffman et al. 2015; Powers et al. 2015; Rosenbaum et al. 2015a,b
Schizophrenia	↑ Neurocognitive function ↑ Serum BDNF ↑ Short-term memory ↓ Positive and negative symptoms ↓ Anxiety, ↓ or ↔ depression ↑ Mental and physical QoL ↓ Psychotic symptom severity	↓ Behavioral abnormalities and deficits ↑ NMDA receptor and BDNF expression	↑ or ↔ hippocampal volume ↑ N-acetylaspartate to creatine ratio ↑ NMDA receptor expression	Beebe et al. 2005; Acil et al. 2008; Pajonk et al. 2010; Scheewe et al. 2012, 2013a,b; Battaglia et al. 2013; Falkai et al. 2013; Kim et al. 2014a,b; Park et al. 2014; Vancampfort et al. 2014; Kimhy et al. 2015, 2016
Stroke	↑ QoL and ability to perform activities of daily living ↓ Comorbid cardiovascular disease risk ↓ Depressive symptoms ↑ Executive function and memory ↓ Poststroke fatigue ↑ Cognition	↑ Spatial memory recovery ↓ Ischemia-induced cell death	↑ Blood flow ↑ Neurogenesis ↑ BDNF ↓ Myelin damage ↓ Microvessel damage	Stummer et al. 1994; Lee et al. 2003; Ding et al. 2004; Sim et al. 2004, 2005; Ploughman et al. 2005; Quaney et al. 2009; Rand et al. 2010; Chen and Rimmer 2011; Graven et al. 2011; Cumming et al. 2012; Dean et al. 2012; Zedlitz et al. 2012; Billinger et al. 2014; Moore et al. 2014; Ahn et al. 2016; Himi et al. 2016
Substance abuse	↓ Risk of daily smoking ↓ Risk of illicit drug use	↓ Drug (amphetamine, cocaine, nicotine) intake ↓ Drug-seeking behavior during extinction and reinstatement ↑ Cognitive function ↓ Withdrawal signs	↑ Bcl-2 ↑ LTP	Kanarek et al. 1995; Smith et al. 2008; Korhonen et al. 2009; Zlebnik et al. 2010, 2012; Terry-McElrath and O’Malley 2011; Miladi-Gorji et al. 2014; Mokhtari-Zaer et al. 2014; Wang et al. 2014; Sobieraj et al. 2016
Traumatic brain injury	↑ Mood ↑ Gait ↑ Ambulatory status ↑ Aerobic endurance	↓ Susceptibility to seizures ↑ Motor function ↑ Cognitive function	↑ BDNF	Charrette et al. 2016; Mychasiuk et al. 2016; Setkowicz et al. 2016; Weinstein et al. 2016

Aβ, Amyloid β; APP, amyloid precursor protein; IL, interleukin; TNF-α, tumor necrosis factor α; LTP, long-term potentiation; BDNF, brain-derived neurotrophic factor; ACTH, adrenocorticotropic hormone; VEGF, vascular endothelial growth factor; 5-TH, 5-hydroxytryptamine (serotonin) receptors; PV, parvalbumin; CA1, Cornu Ammonis 1; NGF, nerve growth factor; MRI, magnetic resonance imaging; PTSD, posttraumatic stress disorder; NMDA, N-methyl-d-aspartate; QoL, quality of life; Bcl-2, B-cell lymphoma 2.